Oxidant stress in hyperlipidemia-induced renal damage

Abstract

Hyperlipoproteinemia can aggravate glomerulosclerosis and chronic tubulointerstitial (ti) damage in kidneys without primary immunologic disease. We evaluated whether the effect of hyperlipidemia on progression of renal damage differed between kidneys without preexisting glomerular disease and kidneys with mesangioproliferative glomerulonephritis and whether the renal actions of hyperlipidemia were dependent on oxidant-antioxidant balance. Hyperlipidemia was induced by high-fat and high-cholesterol diet in uninephrectomized rats. In rats without glomerulonephritis, hyperlipidemia led to a rise in glomerular and ti generation of reactive oxygen species (ROS). Oxygen radicals were mainly generated by enhanced xanthine oxidoreductase (XO), which rose with protein concentration and activity during hyperlipidemia; concurrently, glomerulosclerosis and chronic ti injury were noticed during hyperlipidemia [ti damage (% of total tubulointerstitium (TI) after 150 days): normolipidemia 0.1 +/- 0% vs. hyperlipidemia 3.4 +/- 0. 9%; P < 0.05]. In mesangioproliferative Thy-1 nephritis, ti injury was significantly accelerated by hyperlipidemia (ti damage after 150 days: normolipidemic Thy-1 nephritis 2.5 +/- 0.6% vs. hyperlipidemic Thy-1 nephritis 12.5 +/- 3.1%; P < 0.05). Antioxidant enzyme activities decreased and XO activity rose markedly in the TI (XO activity in TI after 150 days: normolipidemic Thy-1 nephritis 2.2 +/- 0.5 vs. hyperlipidemic Thy-1 nephritis 4.5 +/- 0.7 cpm/microg protein; P < 0.05). In hyperlipidemic Thy-1 nephritis rats, which had a higher urinary protein excretion than normolipidemic rats, hypochlorite-modified proteins, an indirect measure for enhanced myeloperoxidase activity, were detected in renal tissue and in urine, respectively. During hyperlipidemia, chronic damage increased in renal TI. Enhanced generation of ROS, rise in oxidant enzyme activity, and generation of hypochlorite-modified proteins in renal tissue and urine were noticed. These data suggest that oxidant stress contributed to the deleterious effects of hyperlipidemia on the renal TI.

Protective effect of dietary flavonoid quercetin against lipemic-oxidative hepatic injury in hypercholesterolemic rats

“…Hyperlipidemia led to a rise in the generation of reactive oxygen species (ROS), leading to an increased oxidant stress. It has been reported that oxidants and oxidative modifications do play a major role in permanent tissue damage (Scheuer et al, 2000;Kajikawa et al, 2011). The activities of serum AST, ALT, and G-GT have been increased in animals maintained on HCD compared to control animals (Figure 2), which may be attributed to hyperlipidemia that resulted in liver tissue injury (Amin & Abd El-Twab, 2009).…”

“…Hypercholesterolemia is known to impair endothelial functions that may include reduction of endothelial nitric oxide (NO) production (Zou et al, 2003;Kim et al, 2011). It has been reported that hypercholesterolemia increased generation of oxygen free radicals, which contributed to the deleterious effects on the organ tissues, including blood vessels, liver, and kidney (Scheuer et al, 2000;Zou et al, 2003).…”

Postischemic Acute Renal Failure Is Reduced by Short-Term Statin Treatment in a Rat Model

“…This statin-related effect could lead to a decrease in free radical oxygen levels during ischemia and reperfusion. In other models of renal disease, inhibition of oxidative systems was demonstrated to have marked beneficial effects and to prevent tissue damage (20).…”

Dyslipoproteinemia and Impairment of Renal Function in Diabetic Kidney Disease: An Analysis of Animal Studies, Observational Studies, and Clinical Trials

“…A 4-6 fold increase in serum cholesterol is needed to aggravate pre-existing renal injury [63]. In animal models with less pronounced increases in serum cholesterol, other renal injury was applied to exacerbate the disease [64]. This kind of approach could make it difficult to differentiate between hemodynamic and dyslipoproteinemic effect.…”