Luteolin mitigates potassium dichromate‐induced nephrotoxicity, cardiotoxicity and genotoxicity through modulation of Kim‐1/Nrf2 signaling pathways
Omolola Victoria Awoyomi, Yemisi Dorcas Adeoye, Ademola Adetokunbo Oyagbemi, Temitayo Olabisi Ajibade, Ebunoluwa Asenuga, Idayat Titilayo Gbadamosi, Blessing Seun Ogunpolu, Olufunke Olubunmi Falayi, Fasilat Oluwakemi Hassan, Temidayo Olutayo Omóbòwálé, Oluwatosin Adetola Arojojoye, Olufunke Eunice Ola‐Davies, Adebowale Benard Saba, Adeolu Alex Adedapo, Oluwafemi Omoniyi Oguntibeju, Momoh Audu Yakubu
Abstract
Abstract Environmental and occupational exposure to chromium compounds has become potential aetiologic agent for kidney disease with excessive generation of free radicals, apoptosis, and inflammatory. These pathophysiologic mechanisms of potassium dichromate (K 2 Cr 2 O 7 ) have been well correlated with nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study with 40 healthy rats in four experimental groups: Group A (normal saline), Groups B (30 mg/kg K 2 Cr 2 O 7 ), Group C (Luteolin 100 mg/kg and K 2 Cr 2 O 7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K 2 Cr 2 O 7 30 mg/kg), respectively. Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs), immunohistochemistry of Kidney, injury molecule (Kim‐1), nuclear factor erythroid 2‐related factor 2 (Nrf2), and cardiac troponin I were determined. Administration of K 2 Cr 2 O 7 increased blood pressure parameters in systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, and frequency of micronucleated polychromatic erythrocytes, together with reduction in serum nitric oxide level. Renal Kim‐1 and cardiac troponin I expressions were higher, but lower expressions of renal and cardiac Nrf2 were recorded with immunohistochemical analysis. Pre‐treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented antioxidant mechanisms and serum Nitric oxide level, lowered the expressions of Kim‐1, cardiac troponin I and up‐regulated of both cardiac and renal Nrf2, reduced the frequency of micronucleated polychromatic erythrocytes. Taken together, this study therefore demonstrates the cardioprotective, nephro protective and antigenotoxic effects of Luteolin through antioxidantive and radical scavenging mechanisms.