Protective Effects of Vitamin C on Cisplatin-Induced Renal Damage: A Light and Electron Microscopic Study

Abstract

The present study was performed to investigate whether the chronic administration of antioxidant vitamin C provided morphological protection on cisplatin-induced renal damage. Wistar albino male rats were divided into control and two experiment groups, each consisting of six rats. Cisplatin (5 mg/kg/ month) was administered intravenously to the second and third group for three months. After the first application of cisplatin, vitamin C (8 mg/kg/day) to the third group was administered intramuscular for 3 months. At the end of the third month, the kidney specimens of the all groups were obtained. All of these kidney specimens were processed for light and electron microscopical examination. In the second group, most of the renal corpuscle lost their normal appearance and size, especially in the corticomedullary region. The most obvious changes were encountered in the proximal tubules. These changes were tubular dilation, thickening of basement membrane, loss of brush border, vacuolization, and swollenness of mitochondria in the proximal tubule epithelial cells. In addition, infiltration foci were observed mainly in the cortical region. In the third group, which was administered cisplatin plus vitamin C, although the structural damages and morphometric changes were lessened, mononuclear cell infiltration was still observed. This study suggests that the chronic administration of vitamin C may be of therapeutic benefit on cisplatin nephrotoxicity.

Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats

“…On the other hand, the tubules and liver cells from rats in the CDDP + L-carnitine group were nearly normal in histological architecture, except for a minor desquamation of the kidney and liver epithelial cells. Similar findings were also reported by Yuce et al [44] and Tarladacalisir et al [6], demonstrating the structural changes in the kidney and liver tissues of CDDP-treated animals and its turn back by different agents.…”

“…In the present study, it was shown that treatment with only CDDP caused nephrotoxicity in rats, as evidenced by the high biochemical parameters such as high lipid peroxidation and low antioxidant activity, and by histological changes as well. Many studies have reported similar structural changes in the kidney [6,28,29]. In the same way, CDDP caused severe damage in the liver, such as degenerative hepatocytes and moderate enlargement of sinusoids, which was observed by microscopic examination [30,31].…”

“…Cisplatin (cisdiamminedichloroplatinum II, CDDP) is one of the major therapeutic compounds, widely used for the treatment of various cancer species such as ovarian, lung, and testicular cancers [3,4]. However, its clinical usage in high doses is restricted in practice because of its strong side effects in the liver, the kidneys, and other organs [5,6]. CDDP causes the generation of reactive oxygen species (ROS), depletion of GSH levels, and inhibition of antioxidant enzyme activity in these tissues.…”

“…Nath and Norby [11] reported that CDDP decreased kidney glutathione content and increased lipid peroxidation, that CDDP interacted with DNA in a cell-free system and generated superoxide anions, and that oxidant-scavenging enzymes and assorted antioxidants protected against CDDP-induced renal injury. Thus, the administration of antioxidants such as ebselen [12], vitamin C [6], and selenium [7] before treatment with CDDP has been used to protect against ovary, kidney, and liver toxicities in human and experimental animals.…”

Ascorbic Acid in Cancer: A Renewed Hope?

“…Cisplatin is an important antineoplastic drug used in the treatment of many solid organ cancers and the most important dose limiting toxicity that is seen in a significant number of patients is nephrotoxicity. It has been shown previously that AA, either when administered alone or when used in combination with cisplatin, alleviated this toxicity without altering the chemotherapeutic effects of cisplatin [27][28][29][30][31][32][33]. AA, used at a concentration ranging from 3 mM to 100 mM was also found to reduce doxorubicin-induced cardiomyopathy and paclitaxel-induced toxicity without altering efficacy of the anti-neoplastic effects of these drugs [34][35][36].…”