Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats.

N Ehsan,R Andleeb,G Afzal,S Mahboob,M N Riaz,Z Ahmed,F A Al-Misned,A Ashraf,K A Al-Ghanim,S Sarwar,M U Ijaz,A Samad

doi:10.1590/1519-6984.243438

Abstract

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Highlights

Cisplatin (CP) is a chemotherapeutic medicine, used to cure many types of tumors efficiently such as ovarian, head, and neck tumor and testicular sarcoma (Terada et al, 2013)
Though numerous mechanisms have been examined for nephrotoxicity caused by CP, including inflammation and oxidative stress, the precise mechanism has not yet been well understood (Malik et al, 2016)
Casticin is considered as one of the major compounds extracted from herbs (Vetrix and Viticis Fructus), and Asian countries have been using it as traditional medicine extensively since old times (Mali and Dhake, 2011)

Summary

Introduction

Cisplatin (CP) is a chemotherapeutic medicine, used to cure many types of tumors efficiently such as ovarian, head, and neck tumor and testicular sarcoma (Terada et al, 2013). CP causes ROS generation and tubular inflammation, which lead to nephrotoxicity (Yang et al, 2015; Kumar et al, 2017). The main reason behind renal tubular damage is cisplatin-induced oxidative stress (Oh et al, 2017a; Saral et al, 2016). The reactive oxygen species (ROS) and reactive nitrogen species (RNS) changes the cellular structure and function (Pedraza-Chaverri et al, 2004; Divya et al, 2016). Though numerous mechanisms have been examined for nephrotoxicity caused by CP, including inflammation and oxidative stress, the precise mechanism has not yet been well understood (Malik et al, 2016)

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Conclusion