Neuroprotective effect of clavulanic acid on trimethyltin (TMT)-induced cytotoxicity in PC12 cells.

Trimethyltin (TMT) is a short-chain trialkyltin with various applications in industry. In addition, it is a known neurotoxin, producing significant and selective neurodegeneration in the limbic system of both human and animals. Recently, effect of clavulanic acid (CA) in nervous system has been mentioned. Therefore, in this study, the role of CA in TMT-induced toxicity in PC12 cells was evaluated. For this study, PC12 cells were cultured and exposed to different concentrations of CA for 24 h. Then, TMT (20 µM) was added to cells. After that, MTT test was performed to assay cytotoxicity. Reactive oxygen species production (ROS) was determined using 2,7-dichlorofluorescein diacetate (DCFH-DA) method. Additionally, the levels of Bax, Bcl-2, caspase-3, CERB and p-CREB proteins were evaluated using Western blot analysis. The exposure of PC12 cells to TMT reduced cell viability, increased intracellular ROS production, elevated Bax/Bcl-2 ratio and enhanced the expression of caspase-3 (Pro and cleaved forms) protein. Pretreatment of cells with CA before TMT, significantly reduced ROS generation, diminished upregulation of proapoptotic Bax protein and attenuated caspase-3 protein expression. In conclusion, CA exhibited significant neuroprotective effects against neurotoxicity of TMT mainly throughout reduction of ROS production and regulation of proteins, which are involved in apoptosis pathway.

Protective effects of Vitis vinifera (grapes) and one of its biologically active constituents, resveratrol, against natural and chemical toxicities: A comprehensive review.

Vitis vinifera (grape) is one of the "most-produced fruit" in the world. Grape seeds are a valuable source of phenolic compounds including resveratrol (RSV). Grape and one of its biologically active constituents, RSV, exert their protective effects against different natural or chemical toxins which could alter physiological homeostasis through a variety of mechanisms. Some of these mechanisms of actions include increase in superoxide dismutase, hemeoxygenase-1, and glutathione peroxidase activities and reduced glutathione content and decrease in malondialdehyde (MDA) levels and activation of the nuclear erythroid2-related factor2/ARE pathway. There are also various reports of the potential use of such compounds in preventing different ailments including cardiovascular diseases, cancer, degenerative diseases, and inflammatory disorders. Therefore, in this review, we have investigated the possible protective effects of grape and one of its biologically active constituents, RSV, on different organs' toxicity induced by natural toxins (such as mycotoxins, lipopolysaccharide, and triptolide) and chemical toxins (such as antitumors, metals, and carbon tetrachloride). There are insufficient clinical trials on this subject, so our review only includes in vivo and in vitro studies. To establish the grape beneficial effects in human intoxication, more clinical trials need to be accomplished.