Abstract

<p><strong>Objective: </strong>Cisplatin<strong> (</strong>CIS) consumption has become a common problem that affects the health of patients around the globe. Kidney has been suspected to be particularly susceptible to the destructive effects of CIS and nephrotoxic effects are still contentious which in turn affects the Quality of Life (QoL) of patients and increase the mortality rate. This study was conducted to investigate the nephroprotective effect of Noni Juice (NJ) and Divine Noni Gold (DNG) as herbal medicine with established antioxidant properties against the controversial nephrotoxic effect of CIS in mice.</p><p><strong>Methods: </strong>Mice were divided into four groups, each group contained six mice. Group I was kept as normal, Group II received CIS (5.0 mg/kg b. wt. i. p.) on day one for 14 d. <strong>G</strong>roup III and IV received NJ (0.35 ml/mouse p. o.) and DNG (0.35 ml/mouse p. o.) respectively once daily for 14 d, Group V received CIS (5.0 mg/kg b. wt. i. p.) on day one and NJ (0.35 ml/mouse p. o.) once daily for 14 d. Similarly, Group VI received CIS (5.0 mg/kg b. wt. i. p.) on day one and DNG (0.35 ml/mouse p. o.) once daily for 14 d. On day 15 blood from all the mice was collected from the carotid vein and cardiac puncture routes, and the biochemical markers viz. lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), urea were assessed. Kidney from all the animals was isolated, and catalase (CAT), glutathione (GSH), superoxide dismutase (SOD), thiols and lipid peroxidase (LPO) were estimated.</p><p><strong>Results: </strong>CIS-induced marked kidney injury; congestion of tubules, glomerular distortion foci, thickened and blocked blood vessels. Also showed significant elevation of LDH, CPK, and urea with significant inhibition of CAT, GSH, SOD, thiols activities and simultaneously elevation of LPO level. Co-administration of NJ and DNG respectively with CIS protected kidney tissues via oxidative stress inhibition.</p><p><strong>Conclusion: </strong>NJ and DNG possess protective effect against CIS-induced cellular damage in the kidney by decreasing the level of serum biochemical markers, enhancing the level of enzymatic and non-enzymatic antioxidants and maintaining the LPO level. Results suggest that NJ and DNG have strong nephroprotective effect against CIS-induced nephrotoxicity.</p>

Highlights

  • CIS is an antineoplastic agent, widely used in various human malignancies which include head, neck, lung, ovary, bladder, testis, and cervical areas [1]

  • All the values are mean±SEM of six mice, ***ap

  • DNG showed a more protective effect when compared to NJ in both serum biochemical markers and endogenous enzymatic and nonenzymatic antioxidants

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Summary

Introduction

CIS is an antineoplastic agent, widely used in various human malignancies which include head, neck, lung, ovary, bladder, testis, and cervical areas [1]. DNA damaging agents have less toxicity on nonproliferating cells, yet the proximal tubule cells are selectively damaged by CIS because of its accumulation in the kidney to a greater extent compared to other organs [5]. Suggests that this injury is due to inflammation, oxidative stress and apoptosis [6]. Various studies have reported that signaling pathways are involved in modulating cell survival or apoptosis in response to DNA damage induced by CIS [9] and these signaling pathways can be activated by oxidative stress and lipid peroxidation [10, 11]. Reactive Oxygen Species (ROS) may produce cellular injury and necrosis via several mechanisms including peroxidation of membrane lipids, denaturation of protein and DNA damage [12]

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