Intraperitoneal administration of butyrate prevents the severity of acetic acid colitis in rats

Intrarectal infusion of butyrate improves colorectal disorders including ulcerative colitis （UC）. However, it is not established whether systemically administered butyrate benefits such patients. The current study aimed at ex- ploring and comparing the potential of intraperitoneally, intrarectally, and orally administered butyrate against acetic acid （AA）-induced UC in rats. Intrarectal administration of 2 ml of 50% AA was done after or without prior treatment of rats for 7 consecutive days with 100 mg/kg sodium butyrate （SB） intraperitoneally, intrarectally, or orally. Rats were sacrificed after 48 h of hA-treatment. Subsequently, colon sections were processed routinely for histopathological examination. We clinically observed diarrhea, loose stools, and hemoccult-positive stools, and histologically, epithelial loss and ulceration, crypt damage, goblet cell depletion, hemorrhage, and mucosal infiltration of inflammatory cells. The changes were significantly reduced by intraperitoneal, intrarectal, or oral butyrate, with intraperitoneal butyrate exhibiting the highest potency. It is concluded that intraperitoneal administration of butyrate abrogates the lesions of hA-induced UC and its potency surpasses that of intrarectal or oral butyrate.

History of intraperitoneal platinum drug delivery for ovarian cancer and its future applications

Intraperitoneal(IP)delivery of cisplatin was developed in the 1970s based on a strong pharmacologic rationale and rodent models.Its advantage over intravenous(IV)administration was supported initially by observational studies in treating recurrent ovarian cancer and eventually by better outcomes from IP vs.IV cisplatin in randomized studies in patients undergoing optimal surgical debulking at diagnosis.In the past two decades,with the introduction of novel anticancer interventions(such as taxanes,bevacizumab,inhibitors of DNA repair,and immune check point inhibitors),advantages of IP drug delivery are less clear and concerns are raised on cisplatin's therapeutic index.The discovery of BRCA genes and their key role in DNA repair,on the other hand,have strengthened the rationale for IP drug delivery:high grade serous cancers arising in the Mullerian epithelium in association with hereditary or somatic BRCA function inactivation are linked to peritoneal spread of cells that-while initially sensitive-are prone to emergence of platinum resistance.Therefore,selection of patients based on genomic features and focusing on the better tolerated IP carboplatin are ongoing.Recent examples of leveraging the peritoneal route include(1)targeting the cell membrane copper transport receptor-that is shared by platinums-by the combination of the proteasome inhibitor bortezomib and IP carboplatin;and(2)enhancing IP 5-fluoro-2-deoxyuridine cytotoxicity when coupled with PARP inhibition.

A novel rat model of fatty organ degeneration induced by poloxamer 407

Traditional methods of inducing hyperlipidemia in animal models are either costly(genetic manipulation)or it is difficult to control for the effects of other variables.For example,during high-fat feeding,the amount of high-fat diet intake per animal cannot be precisely controlled.The aim of this study was to develop an experimental model of fatty organ degeneration induced by poloxamer 407(P-407).The study was conducted in 2-month-old,male Sprague-Dawley rats that were administered intraperitoneally with either 10%(w/w)P-407(1 g/kg)or saline(10 mL/kg)for 4 months.Their lipid profile,organ degeneration due to fat deposition,and body mass were assessed.Intraperitoneal administration of P-407 resulted in significant increases in plasma triglycerides(P
0.001),total cholesterol(P<0.001),high-density lipoprotein-cholesterol(P
0.001),and low-density lipoprotein(P<0.001)cholesterol.In contrast to the control group,fatty tissue degeneration was observed in the liver,spleen,and kidneys of P-407-treated rats.Positive correlations between fatty tissue degeneration,and the atherogenic index of plasma(P<0.001)and the ratio of total cholesterol to high-density-lipoprotein(P<0.001)were identified.In addition,treatment with P-407 for 3 to 4 months caused a significant reduction in body mass relative to controls(P<0.001).Thus,this study describes the development of a cost-effective experimental rat model of organ degeneration,characterized by fat accumulation in the liver,spleen,and kidneys,which could be used for the study of steatosis and related diseases arising from sustained untreated dyslipidemia.Furthermore,both the atherogenic index of plasma and the ratio of total cholesterol to high-density lipoprotein-cholesterol can be used to predict the risk of fatty tissue degeneration in this model.The study was approval of the University of Jishou Biomedical Research Ethics Committee,China.