Luteolin Attenuates Glycerol-Induced Acute Renal Failure and Cardiac Complications Through Modulation of Kim-1/NF-κB/Nrf2 Signaling Pathways.

Acute renal failure (ARF) has been documented as a life-threatening disease with high morbidity and mortality. We investigated the protective effect of Luteolin against ARF. In this study, forty-male Wistar albino rats were randomly divided into four groups (n = 10). Group A received normal saline. Group B received glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Groups C and D were pretreated with Luteolin 100 and 200 mg/kg for 7 days, and thereafter administered Glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Administration of glycerol significantly increased systolic blood pressure, diastolic blood pressure and mean arterial pressure. Renal protein carbonyl and xanthine oxidase increased significantly while significant reduction in the activity of renal glutathione peroxidase, glutathione S-transferase and glutathione reductase was observed in the glycerol intoxicated rats. Furthermore, administration of glycerol led to significant increases in serum creatinine and blood urea nitrogen together with reduction in nitric oxide (NO) bioavailability. Immunohistochemistry revealed that glycerol intoxication enhanced expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin (CTnI). However, Luteolin pretreatment normalized blood pressure, reduced markers of oxidative stress, renal damage, and improved NO bioavailability. Luteolin also downregulated the expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin. Together, Luteolin might open a novel therapeutic window for the treatment of acute renal failure and cardiac complication.

Antihypertensive Effect of Polyphenol-Rich Fraction of Azadirachta indica on Nω-Nitro-L-Arginine Methyl Ester-Induced Hypertension and Cardiorenal Dysfunction.

Azadirachta indica (AI) is a medicinal plant with reported antioxidant and cardio-protective properties. The use of plant-based polyphenols has become greatly increased in the last one decade. The present study investigated the protective effect of the polyphenol-rich fraction (PRF) of the methanol-extract of Azadirachta indica against Nω-Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal dysfunction in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered potable water. Groups B-E received orally, 40 mg/kg of L-NAME only, 40 mg/kg of L-NAME and 100 mg/kg of AI extract, 40 mg/kg of L-NAME and 200 mg/kg of AI extract, and 40 mg/kg of L-NAME and 25 mg/kg of captopril, respectively for 21 days. The results of the present study revealed that L-NAME administration led to a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Markers of oxidative stress (malondialdehyde,protein carbonyl) increased significantly while there was reduction in reduced glutathione level, activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well nitric oxide bioavailability. Immunohistochemistry revealed higher expressions of nuclear factor kappa beta (NF-kB) and kidney injury molecule 1(Kim-1) and lower expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) in hypertensive rats. Our results indicated that with PRF of AI restored high blood pressure, reduced markers of oxidative stress, normalized serum NO bioavailability and increased the expressions of Nrf2. Hence, PRF of Azadirachta indica could be used for the treatment of hypertension.

Luteolin-mediated Kim-1/NF-kB/Nrf2 signaling pathways protects sodium fluoride-induced hypertension and cardiovascular complications.

The use of sodium fluoride (NaF) as a major ingredient for tooth paste, mouth wash, and mouth rinse has become inevitable in our day-to-day life. However, flavonoids such as Luteolin might be of great value in the prevention of toxicity associated with accidental or inevitable ingestion of NaF. In the study, 40 male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group and received normal saline, Group B was exposed to NaF at 300 ppm (300 mg/L) in drinking water daily for a week, Groups C and D were exposed to 300 ppm (300 mg/L) of NaF and coadministered with Luteolin orally daily at a dosage of 100 mg/kg and 200 mg/kg for the same time point. Our results indicated that NaF caused significant increases in systolic blood pressure, diastolic blood pressure, mean arterial pressure, malondialdehyde, protein carbonyl, myeloperoxidase, advanced oxidative protein products, together with significant reductions in glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and nitric oxide (NO) bioavailability. The electrocardiogram results showed that NaF alone caused significant prolongation of QT and QTc intervals. Immunohistochemistry revealed that NaF caused increase expressions of Kidney injury marker 1 (Kim-1), nuclear factor kappa bet (NF-κB), nuclear factor erythroid 2-related factors 2 (Nrf2), and cardiac troponin I (CTnI). Together, Luteolin coadministration with NaF improved NO bioavailability, reduced high blood pressure, markers of oxidative stress, reversed prolongation of QT and QTc intervals, and lowered the expressions of Kim-1, NF-κB, and CTnI. © 2018 BioFactors, 44(6):518-531, 2018.

Ameliorative effect of Rutin on sodium fluoride-induced hypertension through modulation of Kim-1/NF-κB/Nrf2 signaling pathway in rats.

Sodium fluoride is one of the neglected environmental contaminants. Inorganic fluorides in the environment are found in the air, water, and land. In the study, forty-male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group which was given normal saline, Group B was exposed to 300 ppm of NaF in drinking water, while Groups C and D received NaF along Rutin (100 mg/kg and 200 mg/kg) orally daily for a week. Administration of NaF alone led to significant increases in blood pressure, and deceased serum nitric oxide. Immunohistochemistry revealed higher expressions of kidney injury molecule I (Kim-1), nuclear factor kappa beta (NF-κB), and down regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in rats administered NaF. Rutin co-treatment with NaF normalized blood pressure, lowered Kim-1 and NF-κB expressions, and improved nitric oxide bioavailability.

Quercetin attenuates hypertension induced by sodium fluoride via reduction in oxidative stress and modulation of HSP 70/ERK/PPARγ signaling pathways.

Hypertension is one of the silent killers in the world with high mortality and morbidity. The exposure of humans and animals to fluoride and/or fluoride containing compounds is almost inevitable. This study investigated the modulatory effects of quercetin on sodium fluoride (NaF)-induced hypertension and cardiovascular complications. Forty male rats were randomly separated into four groups (n =10). Group A animals served as the control, rats in Group B were exposed to 300 ppm of NaF, Groups C and D animals were exposed to 300 ppm of NaF along with quercetin orally at 50 mg/kg and 100 mg/kg orally by gavage, while NaF was administered in drinking water, respectively, for a week. Administration of NaF caused severe hypertension as indicated with significant increases in the systolic, diastolic, and mean arterial blood pressure, together with prolonged ventricular depolarization (QRS) and the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT) intervals when compared with controls. NaF significantly decreased the activities of antioxidant enzymes, caused increase in markers of oxidative stress and renal damage when compared with controls. Immunohistochemical staining revealed lower expressions of Hsp70, ERK, and PPARγ in the heart, kidney, and aorta of rats-administered NaF relative to the controls. Together, quercetin co-treatment with NaF restored blood pressure, normalized QRS interval, and improved antioxidant defense system. © 2018 BioFactors, 44(5):465-479, 2018.

Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid.

Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) content. Malondialdehyde, hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also significantly (p<0.05) elevated following DZN exposure. DZN further caused a significant (p<0.05) decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05) in packed cell volume (PCV), hemoglobin concentration (Hb), red blood cell (RBC) count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.