Modulatory effect of Luteolin on potassium dichromate‐induced nephrotoxicity, cardiotoxicity and genotoxicity via Kim‐1/Nrf2 signaling pathways

Abstract

Environmental and occupational exposure to chromium compounds has become a potential aetiologic agent for kidney disease through excessive generation of free radicals, induction of apoptosis and exaggerated inflammatory responses. These are some pathophysiologic mechanisms of potassium dichromate (K2Cr2O7) toxicity with attendant nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study as described; Group A (normal saline), Groups B (30 mg/kg K2Cr2O7), Group C (Luteolin 100 mg/kg and K2Cr2O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2Cr2O7 30 mg/kg), respectively.Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs) were determined. Immunohistochemistry of Kidney Injury molecule (Kim‐1), nuclear factor erythroid 2‐related factor 2 (Nrf2), and cardiac troponin I (CTnI) were also determined.Our results showed that administration of K2Cr2O7increased systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, the frequency of micronucleated polychromatic erythrocytes together with a significant reduction in serum nitric oxide bioavailability.Immunohistochemical staining revealed higher expression of renal Kim‐1 and cardiac troponin I in rats intoxicated with K2Cr2O7. However, lower expression of renal and cardiac Nrf2 were also observed in Luteolin co‐administered rats. Furthermore, co‐treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented in vivo antioxidant status and improved serum NO levels. Lowered expressions of Kim‐1, CTnI and up‐regulation of both cardiac and renal Nrf2, and reduced frequency of micronucleated polychromatic. Taken together, this study demonstrates for the first time the antihypertensive, cardioprotective, nephroprotective and antigenotoxic effects of Luteolin against potassium dichromate induced‐toxicity through antioxidant and radical scavenging mechanisms.