Neuroprotective effect of N-acetylcysteine against cisplatin-induced toxicity in rat brain by modulation of oxidative stress and inflammation

Wessam M Abdel-Wahab,1,2 Farouzia I Moussa1 1Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt; 2Department of Basic Sciences/Biology Unit, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahaman Bin Faisal University, Dammam, Saudi Arabia 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), NAC100 group (100 mg/kg), CDDP group (8 mg/kg), NAC50-CDDP group (50 mg/kg NAC and 8 mg/kg CDDP), and NAC100-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. Keywords: cisplatin, neurotoxicity, brain, N-acetylcysteine, rat

Synergistic protective effect of N-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats

Wessam M Abdel-Wahab,1,2 Farouzia I Moussa,2 Najwa A Saad3 1Department of Biology, College of Medicine, University of Dammam, Dammam, Saudi Arabia; 2Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt; 3Department of Zoology, Faculty of Science, University of Benghazi, Benghazi, Libya Abstract: 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. Keywords: cisplatin, nephrotoxicity, oxidative stress, N-acetylcysteine, taurin

Non-conforming multipatches for NURBS-based finite element analysis of higher-order phase-field models for brittle fracture

This paper proposes an effective computational tool for brittle crack propagation problems based on a combination of a higher-order phase-field model and a non-conforming mesh using a NURBS-based isogeometric approach. This combination, as demonstrated in this paper, is of great benefit in reducing the computational cost of using a local refinement mesh and a higher-order phase-field, which needs higher derivatives of basis functions. Compared with other approaches using a local refinement mesh, the Virtual Uncommon-Knot-Inserted Master-Slave (VUKIMS) method presented here is not only simple to implement but can also reduce the variable numbers. VUKIMS is an outstanding choice in order to establish a local refinement mesh, i.e. a non-conforming mesh, in a multi-patch problem. A phase-field model is an efficient approach for various complicated crack patterns, including those with or without an initial crack path, curved cracks, crack coalescence, and crack propagation through holes. The paper demonstrates that cubic NURBS elements are ideal for balancing the computational cost and the accuracy because they can produce accurate solutions by utilising a lower degree of freedom number than an extremely fine mesh of first-order B-spline elements