Background Neurotoxicity is a major obstacle to the effectiveness of cisplatin (CDDP) in cancer chemotherapy. Oxidative stress and inflammation are considered to be the major mechanisms involved in CDDP-induced neurotoxicity. The rationale of our study was to investigate the efficacy of N -acetylcysteine (NAC) at two different doses in the management of CDDP-induced toxicity in rat brain by monitoring its antioxidant and anti-inflammatory effects. Methods Thirty-five male rats were divided into five groups (n=7) as follows: control group (0.5 mL saline), NAC 100 group (100 mg/kg), CDDP group (8 mg/kg), NAC 50 -CDDP group (50 mg/kg NAC and 8 mg/kg CDDP), and NAC 100 -CDDP group (100 mg/kg NAC and 8 mg/kg CDDP). NAC was administered for 20 consecutive days, while CDDP was injected once on day 15 of the treatment protocol. Results The neurotoxicity of CDDP was evidenced by a marked increase in acetylcholinesterase and monoamine oxidase activities. It also induced oxidative stress as indicated by increased levels of lipid peroxidation, nitric oxide, and protein carbonyl with a concomitant decline in reduced glutathione, glutathione peroxidase, glutathione S-transferase, superoxide dismutase, and catalase in the brain. Moreover, CDDP enhanced the synthesis of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. Treatment with NAC at the two selected doses significantly attenuated CDDP-induced changes in the brain cholinergic function, improved the brain oxidant/antioxidant status, and also reversed the overproduction of pro-inflammatory cytokines in brain and serum. Conclusion NAC could serve as an appropriate and safe complementary therapeutic agent to attenuate the toxicity of CDDP in the brain and therefore improve its outcomes in chemotherapy.

Cisplatin (cis-diaminedichloroplatinum II; CDDP) is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N-acetylcysteine (NAC) and taurine (TAU), both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6) as follows: 1) control group, 2) NAC group, 3) TAU group, 4) NAC–TAU group, 5) CDDP group, 6) CDDP–NAC group, 7) CDDP–TAU group, and 8) CDDP–NAC–TAU group. Cisplatin was administered as a single intraperitoneal injection at a concentration of 6 mg/kg. Three days after CDDP administration, NAC (50 mg/kg) and/or TAU (50 mg/kg) were administered three times weekly for four consecutive weeks. Kidney function markers in serum, urinary glucose and protein, as well as oxidant and antioxidant parameters in renal tissue were assessed. Administration of CDDP significantly elevated urinary glucose and protein, as well as serum creatinine, urea, and uric acid. Moreover, CDDP enhanced lipid peroxidation and suppressed the major enzymatic antioxidants in the kidney tissue. Treatment with NAC or TAU protected against the alterations in the serum, urine, and renal tissue when used individually along with CDDP. Furthermore, a combined therapy of both was more effective in ameliorating CDDP-induced nephrotoxicity, which points out to their synergistic effect.

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An investigation of the influence of dietary calcium (0.3% and 2.7) on the toxicity of dietary lead (50 mg LG 1 ) in the young male rats in a six week period indicated that as dietary calcium increased, the severity of lead toxicity decreased. Evidence include decreased lead concentration in kidney, liver, blood, brain and femurs, accompanied by a distribunces in essential metal (Ca, Zn, Cu, Fe and Mg) levels in kidney, liver brain, femur muscles and blood.

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