Differential Gender Differences in Ischemic and Nephrotoxic Acute Renal Failure

Abstract

Background/Aims:Recent work has shown that female animals are more resistant to ischemic acute renal failure (ARF) than male animals. The mechanism underlying the gender difference is unclear. Moreover, whether the gender difference holds true for ARF induced by other insults is unknown. This study sought to determine the gender differences in ischemic and nephrotoxic ARF. Methods: Gender differences were tested in two experimental models of ARF. For ischemic ARF, bilateral clamping of renal pedicles was conducted in C57BL/6 and129/Sv mice followed by reperfusion. For nephrotoxic ARF, cisplatin was administered to the animals. Renal function, tissue damage, animal survival, and renal cell apoptosis were examined. Results: Ischemic ARF was significantly ameliorated in female mice, as shown by lower serum creatinine and blood urea nitrogen (BUN). Female mice also showed better renal histology, less apoptosis and caspase activation, and a much better survival rate than male mice following ischemic insult. On the contrary, female mice were more sensitive to cisplatin-induced ARF. In these animals, BUN increased at day 1 following cisplatin injection, while in males BUN increases were not shown until day 3. Higher levels of serum creatinine were also recorded in female mice. Renal histology showed severer necrotic tubular damage in females, although apoptosis and caspase activation appeared similar in both genders. Consistently, male mice survived better than females in the nephrotoxic model. Conclusion: While female mice were resistant to ischemic ARF, they appeared more sensitive to cisplatin-induced ARF. Investigation of the gender differences at the cellular and molecular levels might provide a new area for mechanistic study of ARF.

Regulation of PUMA-α by p53 in cisplatin-induced renal cell apoptosis

“…In C57 mice, one dose of cisplatin induced acute renal failure within a few days (data not shown; Wei et al, 2005). Renal tissues were collected to determine PUMA-a by immunoblot analysis.…”

Gender Differences in the Susceptibility to Renal Ischemia-Reperfusion Injury in BALB/c Mice

“…The kidneys of males are much more susceptible to IRI than those of females. Although gender differences in kidney IRI susceptibility have been characterized in rats (Fekete et al 2004) and mice (Park et al 2004;Wei et al 2005), mechanistically, very limited information is available for the gender differences in kidney IRI. Szabo and colleagues suggested that estrogen might play an important role in protecting females from ischemic ARF by limiting endothelin activation (Müller et al 2002).…”

Renoprotective effect of berberine via intonation on apoptosis and mitochondrial-dependent pathway in renal ischemia reperfusion-induced mutilation

“…3 Despite of the comprehensive alien about cellular and molecular mechanisms of cell injury, it has been considered that necrosis and apoptosis of renal epithelial cells are the upshot of acute renal failure. 26 It has been endorsed that newly identified kidney marker kidney injury molecule-1 (KIM-1) which is customary in urine for an extended phase, nonetheless, can be distinguished in the kidney and urine in numerous animal models of nephrotoxins. 27 During ischemia reperfusion, mitochondria accuses permeability evolution, prompted by assorted circumstances, such as amplified outset of reactive oxygen species (ROS), diminution of antioxidants, modification of pyridine nucleotide fractions, fluctuation of Ca 2+ concentration, and engorge of inorganic phosphate in the prevailing surroundings.…”