Vanadium as a chemoprotectant: effect of vanadium(III)-l-cysteine complex against cyclophosphamide-induced hepatotoxicity and genotoxicity in Swiss albino mice

Abstract

Vanadium is an essential micronutrient for living systems and has antioxidant and genoprotective property. In the present study, the protective role of an organovanadium compound vanadium(III)-L-cysteine (VC-III) was evaluated against hepatotoxicity and genotoxicity induced by cyclophosphamide (CP) (25 mg/kg b.w., i.p.) in Swiss albino mice. Treatment with VC-III (1 mg/kg b.w., p.o.) mitigated CP-induced hepatic injury as indicated by reduction in activities of alanine transaminase, aspartate transaminase, alkaline phosphatase by 1.57-, 1.58- and 1.32-fold in concomitant treatment schedule and by 1.83-, 1.77- and 1.45-fold in pretreatment schedule, respectively, and confirmed by histopathological evidences. Parallel to these changes, VC-III ameliorated CP-induced oxidative stress in liver by 1.46-, 1.26-, 1.32- and 1.42-fold in concomitant treatment group and by 1.95-, 1.40-, 1.46- and 1.73-fold in pretreatment group at the level of H2O2, superoxide, nitric oxide and lipid peroxidation, respectively. VC-III also enhanced activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione (reduced) level in mice liver by 1.46-, 1.37-, 1.29-, 1.44- and 1.45-fold in concomitant treatment schedule and by 1.64-, 1.65-, 1.42-, 1.49- and 1.57-fold in pretreatment schedule, respectively. In addition, the organovanadium compound could efficiently attenuate CP-induced chromosomal aberrations, DNA fragmentation and apoptosis in bone marrow cells and DNA damage in lymphocytes by 1.49-, 1.43-, 1.48- and 1.59-fold in concomitant treatment group and by 1.76-, 1.92-, 1.99- and 2.15-fold in pretreatment group, respectively. Thus, the present study showed that VC-III could exert protection against CP-induced hepatotoxicity and genotoxicity.

Protective Effect of Astragalus polysaccharides on Liver Injury Induced by Several Different Chemotherapeutics in Mice

“…Histological changes including liver congestion, disorganization of hepatic cords and ballooning degeneration could be observed in H&E slides. At the same time we have found a remarkable decrease in body weight gain after mice being treated with CTX, notably in high dose group, implying that hepatotoxicity might have contributed to this weight loss as previously reported (King and Perry, 2001;Basu et al, 2014). In addition, we also discovered that the expression level of apoptosis-related protein caspase-3 increased in the liver of mice after received CTX.…”

“…In fact, research has shown that liver toxicity induced by CTX might be associated with the following mechanisms. CTX is extensively metabolized by the liver cytochrome P450 system, which probably causes sinusoidal obstruction syndrome, resulting in a direct toxic effect on hepatic sinusoidal cells, thus inducing necrosis, obstruction, and obliteration of hepatic veins (de Jonge et al, 2006;Basu et al, 2014). Kebieche et al (2009) investigated for the first time the implications of oxidative stress in liver toxicity induced by EPI via evaluating the redox status in hepatic cells in EPI-treated rats.…”

Vanadium: History, chemistry, interactions with α-amino acids and potential therapeutic applications

“…Vanadium compounds have not only been studied as antidiabetic and insulinomimetic agents, but also for the treatment of parasitic diseases of tropical origin, for cancer and as protectors of tissue damage induced by chemical agents and oxidative stress [2,5,[175][176][177][178][179]. Some vanadium compounds, such as vanadylsulphate, sodium vanadate and peroxidovanadates have shown antitumor activity in experimental models in vitro and in vivo [177][178][179][180][181][182].…”

Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice

“…Acrolein, a toxic metabolite of CP, is responsible for chemically alkylate DNA as well as protein, producing cross-links and thereby inducing cytotoxicity [3]. Experimental evidence suggests that the development of oxidative stress after CP administration leads to decrease in the activities of antioxidant enzymes and increase in lipid peroxidation (LPO) level in liver and lungs of mice [4,5]. In addition, increased ROS production subsequently leads to activation of cells of pulmonary defense system like neutrophils, monocytes, and macrophages causing pulmonary fibrosis [6].…”