Effect of some natural antioxidants on aflatoxin B1-induced hepatic toxicity

Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. This hepatotoxicity is thought to be mediated by their ability to generate reactive oxygen species and cause peroxidative damage. In the present investigation we assessed the ability of some natural antioxidants namely, vitamin E and Se, ß-carotene, silymarin and coenzyme Q10 on aflatoxin B1 (AFB1)-induced hepatotoxicity in a rat model. Alanine and aspartate aminotransferases and alkaline phosphatase (ALP) were found to be significantly increased in the serum of AFB1 administered (250 µg/kg body weight/day for 2 weeks) rats, suggesting hepatic damage. There was a marked increase in the lipid peroxide levels and a concomitant decrease in the hepatic reduced glutathione (GSH) and serum protein thiol (PrSHs) along with a nearly twofold increase in hepatic glutathione-S-transferase (GST) activity. The significant increase in GST may be attributed to its being a phase ?? enzyme that predominately participates in the detoxification of the ultimate electrophilic metabolite AFB1-8, 9 epoxide. On the other hand, no significant change was detected in the activities of glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G-6-PDH), cytochrome creductase and levels of DNA and RNA in the hepatic tissue of AFB1 administered rats. Results also revealed that cotreatment with studied antioxidants offered substantial hepatoprotective effects in the AFB1 administered rats. Moreover, results revealed that vitamin E and selenium combination and ß-carotene are more efficient than coenzyme Q10 and silymarin in modulating the liver antioxidant enzymatic system

Zingiber officinale acts as a nutraceutical agent against liver fibrosis

<p>Abstract</p> <p>Background/objective</p> <p><it>Zingiber officinale </it>Roscoe (ginger) (<it>Zingiberaceae</it>) has been cultivated for thousands of years both as a spice and for medicinal purposes. Ginger rhizomes successive extracts (petroleum ether, chloroform and ethanol) were examined against liver fibrosis induced by carbon tetrachloride in rats.</p> <p>Results</p> <p>The evaluation was done through measuring antioxidant parameters; glutathione (GSH), total superoxide dismutase (SOD) and malondialdehyde (MDA). Liver marker enzymes; succinate and lactate dehydrogenases (SDH and LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP), 5'- nucleotidase (5'NT) and liver function enzymes; aspartate and alanine aminotransferases (AST and ALT) as well as cholestatic markers; alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin were estimated. Liver histopathological analysis and collagen content were also evaluated. Treatments with the selected extracts significantly increased GSH, SOD, SDH, LDH, G-6-Pase, AP and 5'NT. However, MDA, AST, ALT ALP, GGT and total bilirubin were significantly decreased.</p> <p>Conclusions</p> <p>Extracts of ginger, particularly the ethanol one resulted in an attractive candidate for the treatment of liver fibrosis induced by CCl₄. Further studies are required in order to identify the molecules responsible of the pharmacological activity.</p

Does varicocele repair improve conventional semen parameters? A meta-analytic study of before-after data

Purpose The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p<0.001; I2=83.62%, Egger’s p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474–1.706; p<0.001; I2=97.86%, Egger’s p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526–2.121; p<0.001; I2=97.88%, Egger’s p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318–1.968; p<0.001; I2=98.65%, Egger’s p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%–2.153%; p<0.001; I2=98.97%, Egger’s p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%–1.759%; p<0.001; l2=97.98%, Egger’s p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%–1.211%; p<0.001; I2=97.87%, Egger’s p=0.1864. Conclusions The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele. Keywords Controlled before-after studies; Infertility, male; Meta-analysis; Varicocel

Association of CARD10 rs6000782 and TNF rs1799724 variants with paediatric-onset autoimmune hepatitis

Although the pathogenesis of paediatric-onset autoimmune hepatitis (pAIH) remains incompletely understood, genetic variants and environmental factors are known to be involved. Caspase recruitment domain family member 10 (CARD10) is a scaffold protein that participates in a complex pathway activating nuclear factor kappa-B (NFκB) and tumour necrosis factor alpha (TNF-α). This study aimed to investigate the association of CARD10 rs6000782 (g.37928186A > C) and TNF gene promoter rs1799724 (c.-1037C > T) variants with pAIH susceptibility in a cohort of Egyptian children. The research was also extended to assess the relationship of these variants with levels of NFκB-p65 and TNF-α. Fifty-six pAIH patients and 44 age- and sex-matched healthy controls were included. Variant genotyping was performed by polymerase chain reaction (PCR). Serum NFκB-p65 and TNF-α levels were measured using enzyme-linked immunosorbent assays (ELISAs). rs6000782 C and rs1799724 T alleles, separate or in combination, were significantly increased in pAIH patients compared to controls. Serum levels of NFκB-p65 and TNF-α were higher in pAIH differentiating both groups. Moreover, the recessive model of rs6000782 revealed a significant association with the levels of both NFκB-p65 and TNF-α. In conclusion, rs6000782 and rs1799724 variants are potential genetic risk factors for pAIH predisposition, with the former affecting NFκB-p65 and TNF-α levels. Overall, the inflammatory cascade was associated with the degree of liver cell destruction. Clinically, screening and genetic counselling are recommended for relatives of pAIH patients. Keywords: Hepatitis, Autoimmune, Variants, Paediatrics, Cytokines, Tumour necrosis facto