Potential protective effect of grape seed extract against acrylonitrile-induced mutagenicity in rats

Acrylonitrile [ACN], an environmental toxic pollutant, has been detected in drinking water, food products and occupational environment. ACN is reported as a potent in vivo and in vitro mutagen and carcinogen in human and experimental animals. Grape seed proanthocyanidine extract [GSE] is a highly bioavailable biologically active polyphenolic bioflavonoid. It is a potent antioxidant posses a broad spectrum of pharmacological and therapeutic activities against free radicals, DNA damage and oxidative stress. The objective of the present study was to investigate the possible in vivo protective effects of GSE against ACN-induced micronucleus and chromosomal aberrations in male rats. Animals were exposed to a single s/c dose of ACN [115 mg/kg body weight]. Another two groups of animals were pretreated with GSE in a dose of 100 and 200 mg/kg body weight orally for seven consecutive days prior to ACN administration [single s/c dose of 115 mg/kg body weight]. The animals were subjected to cytogenetic analysis in bone marrow by micronucleus induction and chromosomal aberrations assays. The present results indicate that ACN significantly induced micronuclei and chromosomal aberrations. Pretreatment with GSE significantly improved these mutagenic effects in a dose related manner

Antioxidant and hepatoprotective effects of thymoquinone against carbon tetrachloride-induced hepatotoxicity in isolated rat hepatocytes

Herbs are known to play a vital role in the management of various liver diseases. Thymoquinone [TQ] is the bioactive constituent of Nigella sativa seed. The present work was planned to evaluate the potential hepatoprotective effects of TQ against the cytotoxic effects and the oxidative stress induced by carbon tetrachloride [CCl4] in isolated primary rat hepatocytes. Cytotoxicity was determined by assessing cell viability and leakage of cytosolic enzymes, such as lactate dehydrogenase [LDH], alanine transaminase [ALT] and aspartate transaminase [AST]. Oxidative stress was assessed by determining reduced glutathione [GSH] level and lipid peroxidation as indicated by thiobarbituric acid reactive substances [TBARS] production. Exposure of isolated rat hepatocytes to CCl4 [5mM] caused cytotoxicity and oxidative injury, manifested by loss of cell viability and significant increase in LDH, ALT and AST leakages. As well as, CCl4 caused progressive depletion of intracellular GSH content and significant enhancement of TBARS accumulation. Preincubation of hepatocytes with either TQ [1mM] or silymarin [5 mM] which is a known hepatoprotective agent, ameliorated the hepatotoxicity and oxidative stress induced by CCl4, as indicated by significant improve in cell viability, significant decrease in LDH, ALT and AST leakages, significant prevent GSH depletion and significant decrease in TBARS formation as compared to CCl4 alone-treated cells. The present results indicate that CCl4 has a potential cytotoxic effect in rat heptocytes; and TQ can afford a significant protection against CCl4 -induced hepatotoxicity