Experimental research Strain of experimental animals and modulation of nitric oxide pathway: their influence on development of renal failure in an experimental model of hepatorenal syndrome

Abstract

IntroductionPathomechanism of HRS is still poorly understood. The aim of our study was: (1) to test whether different strains of rats could develop typical HRS, and (2) to estimate the influence of activation and inhibition of nitric oxide for development of renal failure in course of HRS.Material and methodsFirst, we used 16 of Wistar and 16 of Sprague-Dawley rats in galactosamine model of HRS. Next, we used 48 of SDR rats, which received saline, N-nitro-L-arginine or L-arginine before and after liver damage. Twenty four hours urine and blood samples were collected 48 h after saline or Ga1N injection. Biochemical parameters were determined in serum or urine and then creatinine clearance and osmolality clearance were calculated. Liver and kidney tissues were collected for histopathological examination.ResultsLiver failure developed in all tested groups with significant increase of bilirubin (p < 0.001), ALT (p < 0.001) and ammonia (p < 0.001). Nevertheless we did not achieve any evidence of renal failure in Wistar, but we found typical renal failure in Sprague-Dawley group with significant decrease in creatinine clearance (p < 0.0012) and increase in concentration of creatinine and urea (p < 0.001) and (p < 0.001) respectively. Inhibition of NOS prevented development of renal failure with significant improvement of GFR both before (p < 0.0017) and after (p < 0.003) Ga1N injection. Injection of L-arginine after Ga1N injection did not caused significant improvement of GFR.ConclusionsOur study showed, that genetic factors might be responsible for development of renal failure in course of HRS and nitric oxide play important role in acute model of this syndrome.

Effect of Nitric Oxide Pathway Regulation on Water/Sodium Balance and Renal Function in a Rodent Model of Acute Liver and Renal Failure

“…Anand et al [ 23 ] presented a model of acute liver and renal failure after Ga1N administration to Sprague-Dawley rats in a standard and repeated manner. The findings of our previous study [ 22 ] also showed that acute functional renal failure can occur as a result of acute liver injury and liver failure after Ga1N administration, despite the absence of any histopathological features of renal injuries. We showed there that the development and the grade of renal failure in experimental HRS models may depend on the genetics of the experimental animals [ 22 ].…”

“…The kidneys are intact both in histological and electron microscopy examination and a renal tubular cell line incubated with Ga1N did not show any nephrotoxic effect [ 23 ]. Within 24–48 h of GalN administration, acute liver injury, acute liver failure, and the resultant acute functional renal failure develop in the experimental animals [ 22 ]. Liver injury and liver failure manifest by accumulation of bilirubin, aminotransferase, and ammonia and decrease in albumin levels.…”

“…To our knowledge, no previous study has examined the role of NO in the development of HRS in acute liver disease models. Our previous studies showed that the congenital factors (i.e., the specific strain of experimental animal) are reliable for development of acute renal failure in the course of an acute liver injury experimental model of HRS induced by galactosamine (Ga1N) [ 22 ]. The purpose of the present study was to determine the effect of stimulation and inhibition of the endogenous NO pathway on 2 factors: (1) the water and sodium balance and (2) the development and degree of renal failure in an animal model of acute HRS induced by Ga1N.…”

The effects of vitamins and selenium mixture against brain tissue induced byd‐galactosamine

“…Few studies have examined the effect of experimental d ‐GalN‐induced acute liver failure in different tissues . Consequently, very little information is available on the effects of d ‐GalN on the brain tissues of rats…”

D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure?

“…Javlé et al [ 10 ] and Makin et al [ 11 ] observed a significant reduction in renal blood flow, in addition to hemodynamic changes in the splanchnic vascular bed following the administration of GAL to rats. We also found that animals rapidly developed functional acute renal failure, the development and the degree of which depended on the strain of animal tested, in addition to acute damage and liver failure, following intoxication with GAL [ 12 ]. However, the previous studies investigated the impact of other factors on the development of ALF and associated complications rather than the ALF model itself.…”