Anti-GST Tag polyclonal antibody

Carbon tetrachloride (CCl4) is a Potential nephrotoxin that causes severe and prolonged chemical toxicity. Investigations have been accomplished on numerous species of genus Artemisia, but the plant Artemisia brevifolia has hardly been used in this respect. The present study was considered to ascertain the effects of "Artemisia brevifolia plant extract" against CCl4 prompted nephrotoxicity in male albino rats. Fortyeight male albino rats were allocated into eight groups containing 6 rats in each. Group I was the control group. Group II was given dimethyl sulfoxide (DMSO) (1 ml/kg) orally. Group III was treated with dissolved CCl4 in olive oil (1 ml/kg). Group IV was given CCl4 + Silymarine. Group V and VI were administered with Artemisia brevifolia extract (150 and 300 mg/kg respectively) + CCl4. Group VII and VIII were provided with only 150 and 300 mg/kg extract of Artemisia brevifolia respectively. Results displayed that CCl4 administration significantly (p < 0.05) reduced the activity of antioxidant enzymes like catalase (CAT), peroxidase (POD), Superoxide dismutase (SOD), glutathione (GSH), glutathione reductase (GSR), glutathione-S-transferase (GST), albumin, creatinine clearance and Comet parameters (head length, % in head) while increased the level of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), urea, creatinine, urobilinogen, urinary proteins and comet parameters (number of comets, tail length, comet length, tail moment, % in tail). The administration of Artemisia brevifolia significantly (p < 0.05) improved the histopathology of renal tissues. The results revealed that Artemisia brevifolia has protective consequences against CCl4 induced kidney damage. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Drug-induced toxicity has, in many cases, been linked to oxidative metabolism resulting in the formation of reactive metabolites and subsequent covalent binding to biomolecules. Two structurally related antipsychotic drugs, clozapine (CLZ) and olanzapine (OLZ), are known to form similar nitrenium ion reactive metabolites. CLZ-derived reactive metabolites have been linked to agranulocytosis and hepatotoxicity. We have studied the oxidative metabolism of CLZ and OLZ as well as two known metabolites of CLZ, desmethyl-CLZ (DCLZ), and CLZ-N-oxide (CLZ-NO), using in vitro rat liver microsomal (RLM) incubations with glutathione (GSH) trapping of reactive metabolites and liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). Reactive metabolite binding to selected standard peptides and recombinant purified human proteins was also evaluated. Bottom-up proteomics was performed using two complementary proteases, prefractionation of peptides followed by LC-HRMS/MS for elucidating modifications of target proteins. Induced RLM was selected to form reactive metabolites enzymatically to assess the complex profile of reactive metabolite structures and their binding potential to standard human proteins. Multiple oxidative metabolites and several different GSH adducts were found for CLZ and OLZ. Modification sites were characterized on human glutathione S-transferase (hGST) alpha 1 (OLZ-modified at Cys112), hGST mu 2 (OLZ at Cys115), and hGST pi (CLZ, DCLZ, CLZ-NO and OLZ at Cys170), human microsomal GST 1 (hMGST1, CLZ and OLZ at Cys50), and human serum albumin (hSA, CLZ at Cys34). Furthermore, two modified rat proteins, microsomal GST 1 (CLZ and OLZ at Cys50) and one CYP (OLZ-modified, multiple possible isoforms), from RLM background were also characterized. In addition, direct effects of the reactive metabolite modifications on proteins were observed, including differences in protease cleavage specificity, chromatographic behavior, and charge-state distributions.