Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice

Abstract

Obesity and its consequences can damage the kidney over time. However, less is known about the impact of developing overweight/obesity during childhood on the kidney in adulthood and the renal impact of a superimposed acute kidney injury (AKI). This study evaluated the effect of obesity induced by a high-fat diet initiated soon after weaning on the adult life of mice and their response to superimposed nephrotoxic effects of cisplatin. C57BL/6 post-weaning mice (3 weeks old) were divided into a control group (CT, n = 12) and a high-fat diet group (HF, n = 12). After 9 weeks, animals were further divided into the following groups: CT, CT treated with a single dose of cisplatin (CTCis, 20 mg/kg, i.p.), HF and HF treated with cisplatin (HFCis). The HF group exhibited higher body weight gain compatible with a moderate obesity. Obese mice presented increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration and proteinuria, without any significant changes in blood pressure and glycemia. AKI induced by cisplatin was exacerbated in obese animals with a 92% reduction in the GFR versus a 31% decrease in the CTCis group; this sharp decline resulted in severely elevated serum creatinine and urea levels. Acute tubular necrosis induced by cisplatin was worsened in obese mice. The HFCis group exhibited robust systemic and intrarenal inflammation that was significantly higher than that in the CTCis group; the HFCis group also showed a higher degree of renal oxidative stress. In conclusion, the moderate degree of obesity induced shortly after weaning resulted in mild early renal alterations, however, obese young animals were prone to develop a much more severe AKI induced by cisplatin.

Histological, Biochemical, and Hematological Effects of Goniothalamin on Selective Internal Organs of Male Sprague-Dawley Rats

“…Recent chemotherapeutic agents are often associated with nephrotoxicity complications leading to minimizing the therapeutic doses and thus to limit the antitumor effect of those agents [47]. Moreover, in a recent study, Ribeiro et al [48] investigated the effect of obesity on the nephrotoxic effects of 20 mg/ kg of body weight of Cisplatin in mice. They found that Cisplatin causes acute renal injury especially to obese mice [48].…”

“…Moreover, in a recent study, Ribeiro et al [48] investigated the effect of obesity on the nephrotoxic effects of 20 mg/ kg of body weight of Cisplatin in mice. They found that Cisplatin causes acute renal injury especially to obese mice [48]. The possible explanation for undetectable renal toxicity of GTN could be due to its anti-inflammatory activity.…”

Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury

“…For example, a phosphodiesterase inhibitor and FDA approved compound, pentoxifylline, can systemically reduce inflammation and suppress synthesis of TNFα, preventing cisplatin nephrotoxicity in vivo [31]. Antioxidants such as Tempol [32], increased physical exercise [155], weight loss [156], and novel inhibitors such as Biochanin A [26] and Fasudil [47] have pleiotropic effects in addition to decreasing TNFα expression, with demonstrated in vivo renoprotective effects against cisplatin-induced AKI.…”

Modeling Diet‐Induced Metabolic Syndrome in Rodents

“…All data presented herein were obtained from refs. [44,54,55,70,72,74,75,78,88,95,96,98,[102][103][104][105][106][107][108][109][110][111]116,[119][120][121][124][125][126][127][128][129][130]132,[134][135][136][137][140][141][142][143][144][147][148][149][150][151][152][153][154]…”

“…All data presented herein were obtained from refs. [44,54,55,70,72,74,75,78,88,95,96,98,102–111,116,119–121,124–130,132,134–137,140–144,147–156,158,159,161,163–171,173–176...…”