Establishment of an acute extraocular muscle injury model in cats

AIM： To describe an acute extraocular muscle injury model in cats. METHODS： Seventy-two cats were randomly divided into 6 groups（12 cats per group）. Cats＇ left lateral recti were clamped using a surgical needle holder with a clamping strength of 2（Groups A and D）, 4（Groups B and E） and 6 kg（Groups C and F）. The right lateral recti were treated as controls. On the 4^（th） and 7^（th） days, hematoxylin eosin（HE） staining, immunohistochemical staining for proliferating cell nuclear antigen（PCNA）, muscle force measurements and ocular alignment changes were performed to evaluate the extent of injuries. RESULTS： The morphological changes were graded as mild, moderate or severe by HE staining in all experiment groups. PCNA immunohistochemical staining indicated repairment of muscle fibers in the damaged area. On the 4^（th） and 7^（th） days after clamping, the injured lateral muscle exhibited an elevated threshold for electric stimulation. The muscle forces among groups 2, 4 and 6 kg injury at 4 d（Groups A, B and C） were statistically significant（P0.05）, respectively. In addition, medial deviation in ocular alignment was also present to various degrees in all groups. CONCLUSION： A cat model of acute extraocular muscle injury can be established by rectus clamping. Different clamping strengths can make different degrees of muscle injury. This model may help the future study in the acute extraocular muscle injury.

Effects of DHRS3 in C2C12 Myoblast Differentiation and Mouse Skeletal Muscle Injury

Myoblast differentiation is an essential process during skeletal muscle development.C2C12 myoblast is a commonly used experimental model to study muscle cell differentiation in vitro.Dehydrogenase/reductase(SDR family)member 3(DHRS3)is a highly conserved member in short-chain alcohol dehydrogenase/reductase superfamily and has been shown to be involved in the metabolism of retinol.Previous experimental results showed that the expression of DHRS3 increased significantly during the differentiation of myoblasts differentiation.However,the effect of DHRS3 on mouse muscle cell differentiation was unclear.The objective of current study was to determine if DHRS3 affected muscle cell differentiation,and if DHRS3 was involved in muscle regeneration.Protein expression was determined by western blot and immunofluorescence analysis.The activation and inhibition of DHRS3 increased and decreased C2C12 myoblast differentiation respectively,which indicated that DHRS3 could affect C2C12 myoblast differentiation.DHRS3 expression was significantly changed during muscle regeneration,with the regeneration of muscle injury,the expression of DHRS3 tended to increase first and then decrease.It suggested that DHRS3 might be involved in muscle regeneration.In summary,this study confirmed the involvement of DHRS3 in C2C12 myoblast differentiation and mouse skeletal muscle regeneration and provided a theoretical basis for further elucidating the molecular mechanism of muscle development.

Ultrasound guided acupotomy in treating rhomboid muscle and serratus posterior superior muscle injury:a case report

Objective:The study intended to show us the effect and safety associated with ultrasound-guidance during acupotomy treatment by a case report.Methods:The research presented a case study using ultrasound-guided acupotomy in back pain.The study took place in the Department of Acupuncture and Moxibustion,China-Japan Friendship Hospital.A 56-year-old woman with paroxysmal right upper back pain for more than 10 years,who was diagnosed as the rhomboid muscle and serratus posterior superior muscle injury.Results:After two acupotomy treatments,the Visual Analogue Score(VAS)of the patient declined from7 to 2.One month later,the pain disappeared and the patient was satisfied with it.Conclusion:Ultrasound guidance can be used to observe the anatomical structures clearly to improve the safety of acupotomy treatment.

Membrane and Subcellular Muscle Injury Are Induced by Single or Multiple Exposure to Cigarette Smoke

Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD). Diaphragm injury is observed in patients with COPD. However, the potential role of smoking in triggering or perpetuating muscle injury is unknown. The present study was aimed at evaluating the potential role of commercial tobacco smoke as a direct cause of skeletal muscle injury in experimental conditions. Seventy Wistar rats (170 - 250 g) were assigned to smoking (n = 49) or non-smoking (n = 21) groups. The smoking groups were submitted to a single or multiple (i.e., five or thirty) daily sessions of cigarette smoking in an inhalatory chamber (time length: 2 h each session). The level of exposure was constant and assessed by CO concentrations (50 ppm) and serum cotinine analysis. Animals submitted to a single smoke exposure and the corresponding controls were euthanized in groups at 0 h, 2 h, 4 h, 24 h or 48 h after completing the exposure. Animals submitted to multiple exposures were euthanized at 0 h after smoking. Samples from vastus lateralis muscle were obtained and processed for assessing cell injury and selected protein expression. Monoclonal anti-albumin antibodies were used to identify muscle fibers with sarcolemmal (membrane) injury. Subcellular muscle injury was assessed using transmission electron microscopy (EM). MyoD, myogenin and α-tubulin were immunodetected using western blot techniques. Exposure to cigarette smoke associated with significant membrane damage (mean relative difference (MRD) with controls: +181%, p = 0.004) and sarcomere disruptions (MRD: +226%, p = 0.001). Expression of MyoD and myogenin (normalized to α-tubulin) were significantly increased at 4 h and remained increased at 48 h post-exposure. We conclude that not only a single but also consecutive exposure to tobacco smoke have acute deleterious effects on peripheral muscle structure. A rapid induction of subrogate markers of skeletal muscle stress and repair processes associates to sarcolemmal and sarcomere damage.

Myoprotective effects of bFGF on skeletal muscle injury in pressure-related deep tissue injury in rats

Background:Pressure ulcers(PUs)are a major clinical problem that constitutes a tremendous economic burden on healthcare systems.Deep tissue injury(DTI)is a unique serious type of pressure ulcer that arises in skeletal muscle tissue.DTI arises in part because skeletal muscle tissues are more susceptible than skin to external compression.Unfortunately,few effective therapies are currently available for muscle injury.Basic fibroblast growth factor(bFGF),a potent mitogen and survival factor for various cells,plays a crucial role in the regulation of muscle development and homeostasis.The main purpose of this study was to test whether local administration of bFGF could accelerate muscle regeneration in a rat DTI model.Methods:Male Sprague Dawley(SD)rats(age 12 weeks)were individually housed in plastic cages and a DTI PU model was induced according to methods described before.Animals were randomly divided into three groups:a normal group,a PU group treated with saline,and a PU group treated with bFGF(10μg/0.1 ml)subcutaneously near the wound.Results:We found that application of bFGF accelerated the rate of wound closure and promoted cell proliferation and tissue angiogenesis.In addition,compared to saline administration,bFGF treatment prevented collagen deposition,a measure of fibrosis,and up-regulated the myogenic marker proteins MyHC and myogenin,suggesting bFGF promoted injured muscle regeneration.Moreover,bFGF treatment increased levels of myogenesis-related proteins p-Akt and p-mTOR.Conclusions:Our findings show that bFGF accelerated injured skeletal muscle regeneration through activation of the PI3K/Akt/mTOR signaling pathway and suggest that administration of bFGF is a potential therapeutic strategy for the treatment of skeletal muscle injury in PUs.

Association between ACTN3 R577X genotype and risk of non-contact injury in trained athletes:A systematic review

Purpose:The aim of this study was to review,systematically,evidence concerning the link between the ACTN3 R577X polymorphism and the rates and severity of non-contact injuries and exercise-induced muscle damage in athletes and individuals enrolled in exercise training programs.Methods:A computerized literature search was performed in the electronic databases PubMed,Web of Science,and SPORTDiscus,from inception until November 2020.All included studies compared the epidemiological characteristics of non-contact injury between the different genotypes of the ACTN3 R577X polymorphism.Results:Our search identified 492 records.After the screening of titles,abstracts,and full texts,13 studies examining the association between the ACTN3 genotypes and the rate and severity of non-contact injury were included in the analysis.These studies were performed in 6 different countries(Spain,Japan,Brazil,China,the Republic of Korea,and Italy)and involved a total participant pool of 1093 participants.Of the studies,2 studies involved only women,5 studies involved only men,and 6 studies involved both men and women.All the studies included were classified as highquality studies(≥6 points in the Physiotherapy Evidence Database(PEDro)scale score).Overall,evidence suggests there is an association between the ACTN3 R577X genotype and non-contact injury in 12 investigations.Six studies observed a significant association between A CTN3 R577X polymorphism and exercise induced muscle damage:2 with non-contact ankle injury,3 with non-contact muscle injury,and 1 with overall non-contact injury.Conclusion:The present findings support the premise that possessing the ACTN3 XX genotype may predispose athletes to a higher probability of some non-contact injuries,such as muscle injury,ankle sprains,and higher levels of exercise-induced muscle damage.

Research in prevention and rehabilitation of hamstring muscle strain injury

Hamstring muscle strain injury is the most common and prevalent injury in sports involving high-speed running,such as American football,Australian football,English rugby,soccer,track and field,and cricket.1Hamstring muscle strain injury also has a high recurrence rate of up to 48%.2The average practice and game time loss due to hamstring injury is between17 and 60 days,contingent on the grade of injury.2Severe hamstring muscle strain injuries,and associated recurrent inju-

Sarcopenia diagnosed using masseter muscle area predictive of early mortality following severe traumatic brain injury

Traumatic brain injury（TBI）represents a global pandemic and is currently a leading cause of injury related death worldwide.Unfortunately,those who survive initial injury often suffer devastating functional,social,and economic consequences.

Magnetic Resonance Imaging and Histopathological Analysis of Experimental Muscle Injuries in a Rabbit

Objective To investigate the correlation of magnetic resonance imaging （MRI） with histopathologica changes, and to evaluate T2 mapping in assessing muscle trauma in a rabbit model of muscle injury. Methods We divided 35 rabbits into seven groups that each represented a different time point after intramuscular hemorrhage and muscle injury. Hemorrhage was created by injecting autologous blood into the left legs, and muscle injury was created by scalpel incision of the biceps femoris of the right legs. At different time points, the rabbits underwent Tl-weighted imaging and T2-weighted imaging （TzWl and T2Wl） and T2 mapping. T2 relaxation times were measured, and the corresponding samples were evaluated for pathological changes. Results After 2 h, the intramuscular hemorrhage model demonstrated an increased signal intensity on both TlWl and T2Wl. Histological examination showed erythrocytes within the muscle bundle. On days 1 and 3, the MRI signals were decreased, and there were no significant changes after day 7. From 2 h to 3 days, the muscle-injury model showed a high signal on both TzWl and T2Wl. Corresponding pathological changes included rupture and edema of muscle fibers, and inflammation. The abnormal signals were reduced on day 7. After day 14, the T2Wl intensity remained high. TlWl showed no abnormal changes, but some models showed a high signal, representing fresh bleeding and fatty tissue. T2 relaxation times were significantly different between the central and marginal regions, and between the marginal and normal regions. Conclusion MRI clearly demonstrates intramuscular hemorrhage and muscle injury, which correlate well with histopathological changes. Tz mapping is useful in assessing the extent of injury.

Time for a paradigm shift in the classification of muscle injuries

Muscle injuries remain one of the most common injuries in sport,yet despite this,there is little consensus on how to either effectively describe or determine the prognosis of a specific muscle injury.Numerous approaches to muscle classification and grading of medicine have been applied over the last century,but over the last decade the limitations of historic approaches have been recognized.As a consequence,in the past 10 years,clinical research groups have begun to question the historic approaches and reconsider the way muscle injuries are classified and described.Using a narrative approach,this manuscript describes several of the most recent attempts to classify and grade muscle injuries and highlights the relative strengths and weaknesses of each system.While each of the new classification and grading systems have strengths,there remains little consensus on a system that is both comprehensive and evidence based.Few of the currently identified features within the grading systems have relevance to accurately determining prognosis.

Myofiber Permeability and Force Production of Rat Muscles Following Eccentric Contractions: The Repeated Bout Effect Depends on the Interval

Past eccentric contraction (ECC)-induced muscle injury reduces the severity of symptoms of subsequent muscle injury;this phenomenon is known as a repeated bout effect (RBE). It has been reported that increases in the duration of the interval between the first and second bouts are linked to weakening of the RBE. However, the histology following the attenuation of the RBE remains unclear. We examined the sustained effects of the second bout with regard to myofiber permeability and muscle force. Sixty-four male rats were randomly assigned to eight groups that varied in the number of exercise sessions and the duration of the interval between the first and second bouts: the non-ECC (Control);the single-injury (Post 1st bout);groups that were allowed to recover for 1, 2, and 4 weeks after a single injury (Pre 2nd bout_1w, Pre 2nd bout_2w, and Pre 2nd bout_4w);and groups that were subjected to second injuries 1, 2, and 4 weeks after the first (Post 2nd bout_1w, Post 2nd bout_2w, and Post 2nd bout_4w). The tibialis anterior was electrically stimulated in each ECC group. Twenty-four hours before muscle sampling, Evans blue dye (EBD) (a marker of myofiber damage) was administered. The maximal isometric contraction tension was measured immediately before sampling. The number of EBD-positive (+) fibers was determined via histological analysis. An RBE was revealed by functional examination at the 1- and 2-week and histological examination at the 1-, 2-, and 4-week time points (P < 0.05). In terms of myofiber permeability, prolongation of the interval before the second bout weakened this effect (P < 0.05). Experiments with 1-, 2-, and 4-week intervals indicated that prolongation of the interval before the second bout weakened the RBE with regard to myofiber permeability.

The effect of hamstring flexibility on peak hamstring muscle strain in sprinting

Background:The effect of hamstring flexibility on the peak hamstring muscle strains in sprinting,until now,remained unknown,which limited our understanding of risk factors of hamstring muscle strain injury(hamstring injury).As a continuation of our previous study,this study was aimed to examine the relationship between hamstring flexibility and peak hamstring muscle strains in sprinting.Methods:Ten male and 10 female college students participated in this study.Hamstring flexibility,isokinetic strength data,three-dimensional(3D)kinematic data in a hamstring isokinetic test,and kinematic data in a sprinting test were collected for each participant.The optimal hamstring muscle lengths and peak hamstring muscle strains in sprinting were determined for each participant.Results:The muscle strain of each of the 3 biarticulated hamstring muscles reached a peak during the late swing phase.Peak hamstring muscle strains were negatively correlated to hamstring flexibility(0.1179 ≤ R2≤ 0.4519,p = 0.001) but not to hip and knee joint positions at the time of peak hamstring muscle strains.Peak hamstring muscle strains were not different for different genders.Peak muscle strains of biceps long head(0.071 ± 0.059) and semitendinosus(0.070 ± 0.055) were significantly greater than that of semimembranosus(0.064 ± 0.054).Conclusion:A potential for hamstring injury exists during the late swing phase of sprinting.Peak hamstring muscle strains in sprinting are negatively correlated to hamstring flexibility across individuals.The magnitude of peak muscle strains is different among hamstring muscles in sprinting,which may explain the different injury rate among hamstring muscles.

Relationships among hamstring muscle optimal length and hamstring flexibility and strength

Background:Hamstring muscle strain injury(hamstring injury) due to excessive muscle strain is one of the most common injuries in sports.The relationships among hamstring muscle optimal lengths and hamstring flexibility and strength were unknown,which limited our understanding of risk factors for hamstring injury.This study was aimed at examining the relationships among hamstring muscle optimal length and flexibility and strength.Methods:Hamstring flexibility and isokinetic strength data and three-dimensional kinematic data for hamstring isokinetic tests were collected for11 male and 10 female recreational athletes.The maximal hamstring muscle forces,optimal lengths,and muscle lengths in standing were determined for each participant.Results:Hamstring muscle optimal lengths were significantly correlated to hamstring flexibility score and gender,but not to hamstring strength.The greater the flexibility score,the longer the hamstring muscle optimal length.With the same flexibility score,females tend to have shorter hamstring optimal muscle lengths compared to males.Hamstring flexibility score and hamstring strength were not correlated.Hamstring muscle optimal lengths were longer than but not significantly correlated to corresponding hamstring muscle lengths in standing.Conclusion:Hamstring flexibility may affect hamstring muscle maximum strain in movements.With similar hamstring flexibility,hamstring muscle maximal strain in a given movement may be different between genders.Hamstring muscle lengths in standing should not be used as an approximation of their optimal lengths in calculation of hamstring muscle strain in musculoskeletal system modeling.

Electroacupuncture at Qìhǎishū (气海俞 BL 24) for 40 cases of adductor muscle of thigh injury

Objective To observe the clinical efficacy of electroacupuncture at Qìhǎishū （气海俞 BL 24） for adductor muscle of thigh injury. Methods Forty cases of adductor muscle of thigh injury were treated with electroacupuncture deeply at Qìhǎishū （气海俞 BL 24）. Results After treatment of 10 days, 31 cases （77.5%） were cured, and the total effective rate was 95.0%. Conclusion Electroacupuncture at Qìhǎishū （气海俞 BL 24） has positive clinical efficacy for adductor muscle of thigh injury.

Effect of Aloe Emodin on Proliferation of Vascular Smooth Muscle Cells after Arterial Injury

Objective: To study the effect of Aloe emodin (AE), an active ingredient of Rhubarb,on the kinetics of proliferation of smooth muscular cells (SMCs) cultured in vitro after rabbit iliac arterial injury. Methods: Forty-eight hours after de-endothelialization (balloon endothelial denudation), the iliac arteries of the Japanese white rabbits were isolated and the smooth muscle cells were cultured primarily.AE was added to culture medium containing 10% fetal calf serum (FCS ). The cultures were pulse-labeled with 3H-TdR and TdR uptake into VSMC were measured and the cell cycle of the cultures were analyzed by using flow cytometer. Results: Compared with control, when the concentration gradient ranged from 10 - 1 to 10-5 g/L, the amount (cpm,count per minute) of 3H-TdR uptake into SMCs has significant differences (P < 0. 05 )and 10 -1 and 10 -2 g/L AE showed strong inhibitory effects on TdR uptake into VSMC and the percentage of inhibition [% inhibition =(cpm without AE-cpm with AE)/cpm without AE] was more than 90%. AE displayed concentration dependent inhibitory effects. The percentage of cells in G0/G1 phase was increased, but the percentage of cells in S phase was decreased in AE group, the transition of SMC cycle phase from G0 to S was blocked.Conclusion: AE is a strong inhibitor to the proliferation of SMCs and the pharmacological action of AE may reduce SMC proliferation in vivo and decrease intimal hyperplasia of restenosis.Original article on CJIM(Chin) 1998; 18(7): 420

Epidemiology of injuries in male and female youth football players:A systematic review and meta-analysis

Background:To conduct a systematic review and meta-analysis of epidemiological data of injuries in male and female youth football players.Methods:Searches were performed in MEDLINE/PubMed,Web of Science,Cochrane Library,and SPORTDiscus databases.Studies were considered if they reported injury incidence rate in male and female youth(≤19 years old)football players.Two reviewers(FJRP and ALV)extracted data and assessed trial quality using the Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)statement and the Newcastle Ottawa Scale.The Grading of Recommendations Assessment,Development,and Evaluation approach determined the quality of evidence.Studies were combined using a Poisson random effects regression model.Results:Forty-three studies were included.The overall incidence rate was 5.70 injuries/1000 h in males and 6.77 injuries/1000 h in females.Match injury incidence(14.43 injuries/1000 h in males and 14.97 injuries/1000 h in females)was significantly higher than training injury incidence(2.77 injuries/1000 h in males and 2.62 injuries/1000 h in females).The lower extremity had the highest incidence rate in both sexes.The most common type of injury was muscle/tendon for males and joint/ligament for females.Minimal injuries were the most common in both sexes.The incidence rate of injuries increased with advances in chronological age in males.Elite male players presented higher match injury incidence than sub-elite players.In females,there was a paucity of data for comparison across age groups and levels of play.Conclusion:The high injury incidence rates and sex differences identified for the most common location and type of injury reinforce the need for implementing different targeted injury-risk mitigation strategies in male and female youth football players.

Response of macrophages in rat skeletal muscle after eccentric exercise

Purpose： Macrophages are known to be important for healing numerous injured tissues depending on their functional phenotypes in response to different stimuli. The objective of this study was to reveal macrophage phenotypic changes involved in exercise-induced skeletal muscle injury and regeneration. Methods： Adult male Sprague-Dawley rats experienced one session of downhill running （16~ decline, 16 m/min） for 90 min. After exercise the blood and soleus muscles were collected at 0 h, 6 h, 12 h, 1 d, 2 d, 3 d, 1 w and 2 w after exercise, separately. Results： It was showed that CD6B＋ M1 macrophages mainly infiltrated into musc｜e necrotic sites at 1-3 d, while CD163＋ M2 macrophages were present in muscles from 0 h to 2 weeks after exercise. Using transmission electron microscopy, we observed activated satellite cells 1 d after exercise. Thl-associated transcripts of iNOS and Cc12 were inhibited post exercise, while COX-2 mRNA was dramatically increased 12 h after running （p 〈 0.01 ）. M2 phenotype marker Arg-1 increased 12 h and 3 d （p 〈 0.05, p 〈 0.01 ） after exercise, and Clecl0a and Mrc2 were up-regulated in muscles 12 h following exercise （p 〈 0.05, p 〈 0.05）. Conclusion： The data demonstrate the dynamic patterns of macrophage phenotype in skeletal muscle upon eccentric exercise stimuli, and M1 and M2 phenotypes perform different functions during exercise- induced skeletal muscle injury and recovery.

Does Acute Improvement in Muscle Recovery with Curcumin Supplementation Translate to Long-Term Training?

Dietary polyphenols,such as curcumin,green tea catechins,and pomegranate extract,may have the ability to enhance the effectiveness of long-term training programs by managing training-induced inflammation.Enhanced recovery may translate to increased capacity to train and perform more effectively.The dietary polyphenol curcumin has been reported to block the action of COX-2 and NF-kB signaling and would allow for increased capacity to train leading to heightened adaptations and the potential for ergogenic outcomes.These actions are very similar to the targeted actions of non-steroidal anti-inflammatory drugs(NSAIDs),but without the side-effects of NSAIDs.This review will compare and contrast the known effects of cur-cumin and identify common design elements between existing studies.Through this critical review of the existing literature it is our goal to establish a set of best practices that could be applied to an athletic population that is interested in using oral curcumin supplementation as a recovery agent.

Minimally invasive lumbar interbody fusion via MAST Quadrant retractor versus open surgery： a prospective randomized clinical trial

In recent years, a variety of minimally invasive lumbar surgery techniques have achieved desirable efficacy, but some dispute remains regarding the advantages over open surgery. This study aimed to compare minimally invasive lumbar interbody fusion via MAST Quadrant retractor with open surgery in terms of perioperative factors, postoperative back muscle function, and 24-month postoperative follow-up results. Methods From September 2006 to June 2008, patients with single-level degenerative lumbar spine disease who were not responsive to conservative treatment were enrolled in this study. Patients were randomized to undergo either minimally invasive surgery （MIS, transforaminal lumbar interbody fusion via MAST Quadrant retractor, 41 cases） or open surgery （improved transforaminal lumbar interbody fusion, 38 cases）. Results The MIS group had longer intraoperative fluoroscopy time than the open surgery group, and the open surgery group had significantly increased postoperative drainage volume and significantly prolonged postoperative recovery time compared with the MIS group （P 〈0.05 for all）. MRI scanning showed that the T2 relaxation time in the multifidus muscle was significantly shorter in the MIS group than in the open surgery group at 3 months after surgery （P 〈0.01）. Surface electromyography of the sacrospinalis muscle showed that the average discharge amplitude and frequency were significantly higher in the MIS group than in the open surgery group （P 〈0.01）. The Oswestry disability index and visual analog scale scores were better at 3, 6, 12 and 24 months postoperatively than preoperatively in both groups. Both groups of patients met the imaging convergence criteria at the last follow-up. Conclusions MIS can effectively reduce sacrospinalis muscle injury compared with open surgery, which is conducive to early functional recovery. In the short term, MIS is superior to open surgery, but in the long term there is no significant difference between the two procedures.

A clinically relevant combination treatment with doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice

Background and aims:Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity.A combination chemotherapy regimen of doxorubicin(DOX)and cyclophos-phamide(CPS)is employed in treatment of several cancers such as leukemia,lymphoma,and breast cancer.It is not well understood whether a combination therapy with DOX and CPS can induce hepa-totoxicity.We therefore sought to determine whether co-administration of DOX and CPS at their clini-cally relevant doses and frequency results in hepatotoxicity.Methods:Male C57BL/6J mice received one intraperitoneal injection of saline or DOX-2 mg/kg and CPS-50 mg/kg once a week for 4 weeks.After the treatment period,liver histology and various serum bio-markers of hepatotoxicity were assessed.Results:Co-treatment with DOX and CPS did not alter the serum levels of alanine aminotransferase(ALT),alkaline phosphatase(ALP),bilirubin,albumin,globulin,or total protein.Similarly,co-administration of DOX and CPS did not result in a noticeable change in liver histology.However,it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase(AST).Elevated serum AST levels were also associated with increased serum creatinine kinase(CK)levels,suggesting that the elevated serum AST levels are likely due to muscle injury following the co-administration of DOX and CPS.Conclusions:Taken together,our results,for the first time,suggest that co-administration of DOX and CPS,at their clinically relevant doses and frequency does not induce a significant hepatotoxicity in the mice.