Naringenin protects hepato-renal tissues against antituberculosis drugs induced toxic manifestations by modulating interleukin-6, insulin like growth factor-1, biochemical and ultra-structural integrity.

BACKGROUND: The antituberculosis drugs (ATDs), isoniazid, rifampicin, pyrazinamide and ethambutol prompt extreme hepatic and renal damage during treatment of tuberculosis. The present study aimed to investigate protective potential of naringenin against ATDs induced hepato-renal injury. METHODS: Rats were administered with ATDs (pyrazinamide; 210, ethambutol; 170, isoniazid; 85, rifampicin; 65 mg/kg b.wt) orally for 8 weeks (3 days/week) followed by naringenin at three different doses (10, 20 and 40 mg/kg b.wt) conjointly for 8 weeks (3 days/week alternately to ATDs administration) and silymarin (50 mg/kg b.wt) as positive control. RESULTS: Exposure to ATDs caused significant increase in interleukin-6 (IL-6), triglycerides, cholesterol, bilirubin whereas depletion in insulin like growth factor-1 (IGF-1), albumin and glucose in serum. Endogenous antioxidant enzymes glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate-dehydrogenase (G-6-PDH) were diminished in liver and kidney tissues with parallel increase in triglycerides, cholesterol, microsomal LPO and aniline hydroxylase (CYP2E1 enzyme). Ultra-structural observations of liver and kidney showed marked deviation in plasma membranes of various cellular and sub-cellular organelles after 8 weeks of exposure to ATDs. CONCLUSIONS: Conjoint treatment of naringenin counteracted ATDs induced toxic manifestations by regulating IL-6, IGF-1, CYP2E1, biochemical and ultra-structural integrity in a dose dependent manner. Naringenin has excellent potential to protect ATDs induced hepato-renal injury by altering oxidative stress, modulation of antioxidant enzymes, serum cytokines and ultra-structural changes.

Protective activity of purpurin against d-galactosamine and lipopolysaccharide-induced hepatorenal injury by upregulation of heme oxygenase-1 in the RBC degradation cycle.

Acute liver failure, associated with oxidative stress and sustained inflammation is the major clinical manifestation of liver diseases with a high mortality rate due to limited therapeutic options. Purpurin is a bioactive compound of Rubia cordifolia that has been used in textile staining, as a food additive, and as a treatment of multiple chronic and metabolic diseases associated with inflammation and oxidative stress. The present work aimed to investigate the protective efficacy of purpurin against hepatorenal damage. Thirty-six female albino rats were equally assigned into six groups. Purpurin was administered orally once a day for 6 days at doses of 05, 10, and 20 mg/kg, respectively. Intraperitoneal injection of lipopolysaccharide (50 µg/kg) was administered to the animals on 6th day evening, 1 h after d-galactosamine (300 mg/kg) administration to induce hepatorenal injury. The results revealed that purpurin alleviated alterations in serological and hematological parameters as well as restored histoarchitectural and cellular integrity of the liver and kidney. Purpurin restored superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione content in hepatorenal tissues. Accompanied by the diminution of increased bilirubin and biliverdin, purpurin also diminished total cholesterol, triglyceride, and lipid peroxidation in hepatorenal tissues. Purpurin markedly attenuated the elevation of CYP2E1, restored glutathione-S-transferase, and prevented DNA damage in hepatorenal tissues. Purpurin reduced iron overload by reducing heme depletion and recycling of ferritin and hemosiderin. It also reinforced biliverdin reductase, heme oxygenase-1 to employ hepatorenal protection by regulating antioxidant enzymes and other pathways that produced NADPH. Thus, it may be concluded that purpurin has protective potential against acute hepatorenal injury.

Quercetin ameliorates acute acrylamide induced spleen injury.

Acrylamide is used for industrial and laboratory purposes; it also is produced during cooking of carbohydrate-rich food at high temperature. We investigated the therapeutic potential of quercetin for treatment of acute acrylamide induced injury to the spleen. We used female albino rats treated with acrylamide for 10 days followed by oral administration of quercetin in three doses for 5 days. We observed significantly reduced total body weight, spleen weight, red blood cells, total proteins, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phophate dehydrogenase, reduced glutathione, concentration of serum IgG and IgM after acrylamide induced toxicity compared to controls. We also found that white blood cells, triglycerides, cholesterol and lipid oxidation were increased significantly after acrylamide induced toxicity in rats compared to controls. Histoarchitecture of spleen was affected adversely by acrylamide toxicity. Administration of quercetin ameliorated adverse effects of acrylamide in a dose-dependent manner. Quercetin appears to ameliorate acrylamide induced injury to the spleen by increasing endogenous antioxidants and improving histoarchitecture and immune function.

Protective role of rutin against combined exposure to lipopolysaccharide and D-galactosamine-induced dysfunctions in liver, kidney, and brain: Hematological, biochemical, and histological evidences.

Protective efficacy of rutin over liver, kidney, and brain dysfunctions was evaluated in this investigation. Rutin (5, 10, and 20 mg/kg) was administered continuously for 6 days followed by single dose of D-galactosamine (300 mg/kg I.P.) and lipopolysaccharide (50 µg/kg I.P.) on the 6th day. Hematological, serological, biochemical, and histological aspects were considered for this study. One-way ANOVA (p ≤ .05) followed by Tukey's HSD post hoc test determined the statistical significance. Serum AST, ALT, ALP, urea, uric acid, and creatinine were increased significantly, whereas albumin and glucose were significantly decreased after combined exposure to LPS and D-GalN. Glutathione level and activity of SOD and catalase were decreased, whereas lipid peroxidation, triglycerides, and cholesterol were increased in tissue samples due to LPS- and D-GalN-induced toxicity. Prophylactic treatment of rutin maintained studied variables toward control claiming the protective role of rutin. PRACTICAL APPLICATION: Rutin is plenteous in a variety of commonly ingested foods such as onion, wine, grape, citrus fruits, tea, and buckwheat. Rutin supplement is recommended for the treatment of various diseases such as varicose veins, internal bleeding, or hemorrhoids. Rutin is better than well-known antithrombic agent, Juniferdin, or Bacitracin. In the present study, rutin showed protective effects against LPS- and D-GalN-induced multiorgan dysfunctions due to its anti-inflammatory and antioxidant properties. Therefore, rutin may be developed and practiced as a food supplement to cope with acute organ dysfunctions caused by inflammatory and oxidative damage.

Gallic Acid Protects from Acute Multiorgan Injury Induced by Lipopolysaccharide and D-galactosamine.

BACKGROUND: Secondary metabolites of plants, the polyphenols, play a vital role in protection from many health problems in human beings. Structurally favored phytochemicals may be studied to protect multiorgan injury. At pharmacological doses, gallic acid is nontoxic to mammals and is generally absorbed in the intestine. AIMS: In this present study, gallic acid was evaluated for its protective efficacy against Lipo Polysaccharide (LPS) and d-Galactosamine (D-GalN) induced multiorgan injury, i.e., liver, kidney and brain. METHODS: Three different doses of gallic acid (5, 10 and 20 mg/kg p.o.) were administered to the experimental animals for 6 consecutive days, followed by exposure to LPS (50 µg/kg I.P.) and D-GalN (300 mg/kg I.P.) on the 6th day. RESULTS: Exposure to LPS and D-GalN resulted in increased oxidative stress and proinflammatory cytokines. Altered hematology and serology due to LPS and D-GalN were restored towards control by gallic acid. Declined antioxidants such as reduced glutathione, superoxide dismutase and catalase due to injurious effects of LPS and D-GalN were rejuvenated by gallic acid. DISCUSSION: Exposure to LPS and D-GalN severely increased lipid peroxidation, CYP2E1 activity and tissue lipids while lowered protein content. Gallic acid restored all these parameters towards control in dose dependent manner and 20 mg/kg dose provided the best protection. Histological study showed improved histoarchitecture of liver, kidney and brain that supported biochemical endpoints. CONCLUSION: Gallic acid minimized oxidative stress and provided best protection at 20 mg/kg dose against LPS and D-GalN induced multi organ acute injury.