Renal Toxicity of Nickel,Sodium Lauryl Sulphate and Their Combination after Dermal Application in Guinea Pigs

The guinea pigs were dermally exposed to nickel (Ni), sodium lauryl sulphate (SLS) and in their combination for 7 and 14 days. The exposure to Ni and SLS produced changes in enzymes and lipid peroxidation in kidney. The exposure to Ni or SLS depicted slight changes while combined exposure to Ni plus SLS exhibited more degenerative changes in kidney. The result of the study suggests that industrial workers and/or populations exposed simultaneously to Ni and SLS produces more damage to kidney.

Preliminary Evaluation of Hepatorenal Protective Potentials of <i>Kigelia africana</i>Ethanolic Leaf Extract on Carbon Tetrachloride Induced Toxicity in Adult Male Wistar Rats

Background and aim: Hepatorenal toxicity is a very common ailment with resultant deleterious burden on the overall body systems and high mortality rate. Although myriads of drug agents are in circulation, its medical management is still inadequate as no effective treatment which inhibits disease progression and complications, has been synthesized yet. Therefore, this study focused on the potentials of Kigelia africana ethanolic leaf extract (KAELE) in preventing hepatorenal toxicity using CCl4 model of toxicity in rats. Method: KAELE was subjected to phytochemical screening. Following two-week acclimatization, thirty-six (N = 36) adult male Wistar rats were grouped into six consisting of six animals each (n = 6). Group I was given distilled water as control while groups II to VI received silymarin (100 mg/kg), CCl4 (1 ml/kg), KAELE (100 mg/kg, 200 mg/kg and 400 mg/kg) respectively. All groups pre-treated with silymarin and Kigelia africana ethanol leaf extract lasted for a period of fourteen (14) days using a gastric tube. CCl4 was administered intraperitoneally to groups II, III, IV, V and VI 48 hours after the last pretreatment on day 14. Post treatment, animals were sacrificed and the blood obtained and sera used for biochemical analysis while the tissues for histological evaluations. Results: The phytochemical tests revealed the presence of flavonoids, tannins, steroids, terpenoids, saponins, glycosides, alkaloids, and phenols. There was a significant decrease (P < 0.05) in the level of all serum liver enzymes (AST, ALT and ALP) in the extract-treated groups. KAELE showed a dose-dependent hepato-protective property as it significantly mitigated the effects of carbon tetrachloride on the liver function markers studied (total bilirubin, conjugated bilirubin, albumin and total protein). KAELE showed the decrease necrotic hepatic plates around the portal areas and damaged blood vessels with less fatty acids infiltrations in this study. Conclusion: KAELE possesses hepatorenal protective potentials.

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir

BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNA<20 IU/mL,but detectable)were enrolled in the study.The patients were randomly assigned to either continue ETV(0.5 mg)daily or switch to TAF(25 mg)daily for 48 wk.The primary endpoint was the proportion of patients who achieved a virologic response(HBV DNA level<20 IU/mL)at week 48.Secondary endpoints included changes in serum alanine aminotransferase(ALT),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and anti-HBe levels,and renal and bone safety parameters.RESULTS At week 48,the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two groups.None of the patients developed genotypic resistance to ETV or TAF.Both drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse events.No significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either group.The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group(-0.8%vs-2.1%,P=0.004;-0.6%vs-1.8%,P=0.007,respectively).CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.

Endocrine Disruption of Cadmium in Rats Using the OECD Enhanced TG 407 Test System

Objective To evaluate the endocrine disrupting effects of cadmium （Cd） using OECD enhanced TG407 test guideline. Methods Sprague-Dawley （SD） rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg.BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected. Results Cd could significantly decrease animals＇ body weight （P〈0.05）. Serum luteinizing hormone （LH） at 10-20 mg/kg.BW groups and testosterone （T） at 2.5 and 10 mg/kg.BW groups decreased significantly （P〈0.05）. However, no statistically significant change was found in urinary β2-microglobulin among Cd-treatment groups （P〉0.05）. Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg.BW groups showed significant increase （P〈0.05）. While among male rats in 2.5, 10, 20 mg/kg.BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased （P〈0.05）. Moreover, no histopathological change was observed in kidney. Conclusion Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.

Differential effect of aqueous Desmodium gangeticum root extract mediated TiO2 nanoparticles on isolated mitochondria, cells and Wistar rats

Objective: To study the renal toxic effect of titanium dioxide nanoparticles(TiNPs)prepared by chemical and green route.Methods: TiNPs were prepared by chemical(sol gel technique) and green route(using aqueous extract of Desmodium gangeticum root by using titanium tetraisopropoxide as precursor). Thus prepared TiNPs were characterized using UV–visible spectrophotometry, X-ray diffractometry and evaluated its renal toxic impact in different experimental models viz., Wistar rats(100 mg/kg b.wt.; oral), LLC-PK1 cells(100 mg/m L) and isolated renal mitochondria(0.25, 0.5 and 1 mg/m L).Results: Compared to the chemically synthesized TiNPs, Desmodium gangeticum synthesized nanoparticles showed less nephrotoxicity, determined by elevated serum renal markers like urea(62%), creatinine(35%), aspartate aminotransferase(61%) and alanine transaminase(37%) and the result was in agreement with cellular toxicity(measured by MTT assay and lactate dehydrogenase activity). Further toxicity evaluation at the level of mitochondria showed not much significant difference in TiNPs effect between two synthetic routes.Conclusions: The biochemical findings in renal tissue and epithelial cell(LLC-PK1)supported by histopathology examination and isolated mitochondrial activity showed minor toxicity with TiNPs prepared by green route(Ti NP DG) than TiNP Chem.