Cyclophosphamide (CPM), an alkylating agent is used as an immunosuppressant in rheumatoid arthritis and in the treatment of several cancers as well. In this study, Ellagic acid (EA), a naturally occurring plant polyphenol, was evaluated for its antigenotoxicity and antioxidant efficacy against the CPM-induced renal oxidative stress and genotoxicity in Swiss albino mice. The mice were given a prophylactic treatment of EA orally at a dose of 50 and 100 mg/kg body weight (b wt) for seven consecutive days before the administration of a single intraperitoneal (i.p.) injection of CPM at 50 mg/kg b wt. The modulatory effects of EA on CPM-induced nephrotoxicity and genotoxicity were investigated by assaying oxidative stress biomarkers, serum kidney toxicity markers, DNA fragmentation, alkaline unwinding assay, micronuclei (MN) assay, and by histopathological examination of kidney tissue. A single intraperitoneal administration of CPM in mice increased malondialdehyde level with depletion in glutathione content, antioxidant enzymes activities, viz. glutathione peroxidase, glutathione reductase, catalase, quinone reductase, induced DNA strand breaks, and MN induction. EA oral administration at both doses caused significant reduction in their levels, restoration in the activities of antioxidant enzymes, reduction in MN formation, and DNA fragmentation. Serum toxicity marker enzymes like BUN, creatinine, and LDH were also increased after CPM treatment which was significantly decreased in EA pretreated groups. Present findings suggest a prominent role of EA against CPM-induced renal injury, DNA damage, and genotoxicity.
The results of the present study demonstrate that oxidative stress and inflammation are closely associated with cisplatin-induced toxicity and chrysin shows the protective efficacy against cisplatin-induced hepatotoxicity possibly via attenuating the oxidative stress and inflammatory response.
Benzo(a)pyrene (B(a)P) is a well-known environmental contaminant and carcinogen. Its sources include tobacco smoke, automobile exhaust, forest fire, and other combustion processes. Farnesol, an active principle of Vachellia farnesiana and other aromatic plants, possesses preventive properties against various toxicities. Present study was designed to estimate chemopreventive effects of farnesol against B(a)P-induced pulmonary injuries. To determine the protective effects of farnesol, it was administered orally at 2 doses (100 and 200 mg/kg body weight [b.w.]) once daily for 14 days. Rats were exposed intratracheally to B(a)P, 5 mg/kg b.w. on days 12 and 14, thereafter assessed for pulmonary toxicities 24 hours post last dose of B(a)P. B(a)P-induced edema, inflammation, oxidative stress, and consequent damages in lungs were assessed in terms of total protein, total cell count, nitric oxide (NO), lactate dehydrogenase (LDH), alkaline phosphatase, and in bronchoalveolar lavage fluid (BALF). B(a)P also reduced the levels of phospholipids (lung surfactants) in BALF. However, pretreatment with farnesol at both the doses significantly reduced the lung injuries and inflammatory responses. Farnesol also protected the levels of phospholipids to normal when compared with control. It also modified the activities of B(a)P metabolizing enzymes NADPH-cytochrome P450 reductase, microsomal epoxide hydrolase (mEH), and glutathione S-transferase (GST) in lung tissue of rats. Present findings suggest a prominent role of farnesol against B(a)P-induced lung inflammation, edema, surfactant dysfunction, and epithelial damages in Wistar rats. In conclusion, farnesol shows lung protection against B(a)P toxicities in Wistar rats.
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