Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity

Abstract

The world-wide increase in cancer incidence imposes a corresponding significant increase in the use of chemotherapeutic agents. Nephrotoxicity is a side effect frequently encountered with cyclophosphamide (CP), which is also well-known to cause acute and chronic lung toxicities. The current study focuses on the evaluation of the potential protective efficacy of tranilast against acute and subacute CP-induced lung and kidney injuries in male Swiss Albino mice. Intraperitoneal CP significantly impaired oxidant/anti-oxidant balance and increased inflammatory cell count in bronchoalveolar lavage fluid, serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) levels, with significant impairment of lung and kidney architectures. Tranilast taken orally for 8 and 14 days significantly enhanced mice anti-oxidant defense mechanisms; it increased lung and kidney SOD activity, GSH content and reduced lipid peroxidation. Tranilast significantly reduced serum creatinine and BUN. Furthermore, it decreased accumulation of inflammatory cells in the lungs. Serum TNF-α, LDH, total lung and kidney protein contents significantly declined as well. Histopathological examination revealed concomitant significant tissue recovery. Such results show a significant protective potential of tranilast against deleterious lung and kidney damage induced by CP, probably by enhancing host antioxidant defense mechanism, decreasing cytotoxicity, and decreasing expression of inflammatory cytokines.

Antioxidant and Hepatoprotective Effects of Tranilast against Thioacetamide-Induced Liver Fibrosis in Rats

“…This protective effect appeared in the form of significant elevation of liver GSH and SOD with significant depletion of liver MDA compared to TAA group. These results are in agreement with (Said et al 2016) who found that tranilast administration significantly decreased MDA content in lung and kidney homogenates, suggesting decreased lipid peroxidation, generation of ROS and a positive influence on the host antioxidant defenses. Moreover, (Miyachi et al 1987) reported that tranilast significantly reduced all ROS levels and this antioxidant effect was related to its ability to scavenge ROS through direct inhibition of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and/or xanthine oxidase activity.…”

Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice

“…Acrolein interferes with the tissue antioxidant defense system, increases lipid peroxidation and produces ROS [37]. Various studies have consistently demonstrated that CP induces nephrotoxicity by increasing the oxidative stress specifically ROS [5,33,36,38]. These reports have suggested that overproduction of ROS impairs the kidney functions, which is accompanied by increasing in serum Cr and BUN levels.…”

Curcumin Prevents Cyclophosphamide-Induced Lung Injury in Rats by Suppressing Oxidative Stress and Apoptosis

“…CP decreases the activity of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) as well as levels of non-enzymatic antioxidants [4][5][6][7]. At the same time, CP increased the lipid peroxidation product malondialdehyde (MDA) [8] and tumor necrosis factor-α (TNF-α) [9] in the lungs of mice and rats, respectively.…”