Luteolin mitigates potassium dichromate-induced nephrotoxicity, cardiotoxicity and genotoxicity through modulation of Kim-1/Nrf2 signaling pathways.

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 (K2 Cr2 O7 ) 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 K2 Cr2 O7 ), Group C (Luteolin 100 mg/kg and K2 Cr2 O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2 Cr2 O7 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 K2 Cr2 O7 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.

Telferia Occidentalis and Vitamin C Attenuate Phenylhydrazine-Induced Haemolytic Anaemia and Associated Cardio-renal Dysfunctions via Inhibition of Oxidative Stress and Proapoptotic -Protein (Bax) Expressions.

BACKGROUND: The study investigated the modulatory roles of the aqueous leaf extract of Telferia occidentalis, a traditional haematinic, and vitamin C on cardiovascular dysfunction associated with subchronic Phenylhydrazine exposure. METHODS: Fifty adult male rats were randomly selected and divided into one of five groups of ten animals each: Control; 40 mgkg-1 Phenylhydrazine (PHZ); PHZ with 100 mgkg-1 T.occidentalis; PHZ with 200 mgkg-1 T.occidentalis; and PHZ with 100 mgkg-1 vitamin C. RESULTS: Oral exposure of rats to PHZ, without T. occidentalis or vitamin C treatment, resulted in a significant (p<0.05) decrease in the haematological parameters, but increased the blood pressure parameters of rats However, treatment with vitamin C and T. occidentalis leaf extract significantly (p<0.05) ameliorated the aforementioned PHZ-induced alterations of rats haemogram, and blood pressure. Biochemical analysis revealed significant (p<0.05) reduction in the activities of superoxide dismutase and catalase of untreated PHZ-exposed rats, but the levels of malondialdehyde, hydrogen peroxide and myeloperoxidase of the rats were significantly (p<0.05) increased compared with those of the extract treated rats. Immunohistochemical analysis revealed a greater expression of Bax-protein in the cardiac and renal tissues of the untreated PHZ exposed rats, compared with the extract and vitamin C treated groups. CONCLUSIONS: The mitigation of oxidative stress and inhibition of Bax-protein expression are probable mechanisms of action of T. occidentalis in the amelioration of haemolytic anaemia, and its use as adjunct medication in the management of some diseases is justifiable.

Protective Effect of Azadirachta indica and Vitamin E Against Arsenic Acid-Induced Genotoxicity and Apoptosis in Rats.

Sodium arsenite (NaAsO2) is one of the major environmental toxicants with severe toxicological consequences in some developing and developed countries. Rats in Group A received normal saline. Genotoxicity and apoptosis were induced by single intraperitoneal injection of 10 mg/kg sodium arsenite to rats in Groups B-F. Rats in Groups C and D had earlier been pretreated with Azadirachta indica (100 and 200 mg/kg) or E and F with vitamin E (50 and 100 mg/kg), respectively. Markers of oxidative stress, inflammation, hepatic damage, genotoxicity, and apoptosis were assessed. Pretreatment of rats with either Azadirachta indica or vitamin E led to a significant (p <.05) increase in the activities of glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in the liver compared to the group that received NaAsO2 alone. Markers of oxidative stress and inflammation, malondialdehyde (MDA), hydrogen peroxide (H2O2) generation, nitric oxide (NO), and myeloperoxidase (MPO), were significantly (p <.05) lowered in rats pretreated with Azadirachta indica or vitamin E. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) and expression of caspase-3 were significantly (p <.05) reduced in rats pretreated with either Azadirachta indica or vitamin E compared to rats intoxicated with arsenite. Histopathology of the liver showed areas of infiltration of inflammatory cells with deaths of numerous hepatocytes in NaAsO2-intoxicated rats, and these were reversed by Azadirachta indica. Together, we report for the first time the genoprotective and antiapoptotic effect of Azadirachta indica by a significant reduction in the frequency of micronuclei-induced apoptosis and oxidative stress by arsenic intoxication.

Cyclophosphamide-induced Hepatotoxicity in Wistar Rats: The Modulatory Role of Gallic Acid as a Hepatoprotective and Chemopreventive Phytochemical.

BACKGROUND: Gallic acid (GA) is an endogenous plant phenol known to have antioxidant, free radical scavenging ability, anti-inflammatory, anti-cancer, and anti-fungal properties. The aim of this study was to assess the protective effect of GA on cyclophosphamide (CPA)-induced hepatotoxicity in male Wistar rats. METHODS: Sixty rats were grouped into six groups of 10 rats per group. Group 1 received distilled water. Group 2 received CPA at 200 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 received a single dose of CPA (200 mg/kg) intraperitoneally on day 1 and then were treated with GA at 60 and 120 mg/kg body weight for 14 days, respectively. Rats in Groups 5 and 6 only received GA at 60 and 120 mg/kg body weight for 14 days, respectively. GA was administered orally. RESULTS: CPA induced hepatic damage as indicated by significant elevation (P < 0.05) in aspartate aminotransferase, organ weight, and evidence by the histological study. CPA also induced hepatic oxidative stress as indicated by significant elevation (P < 0.05) in malondialdehyde content, hydrogen peroxide (H2O2) generation, nitrite level, and the level of glutathione (GSH) peroxidase crashed in the CPA-treated group. GA enhanced the antioxidant defense system as indicated by significant elevation (P < 0.05) in GSH level, catalase activity, and GSH-S-transferase activity. CONCLUSIONS: Taken together, the result of this present study shows that GA has a protective effect on CPA-induced hepatotoxicity.