Protective Effect Of Rutin Research Articles

Protective Effect of Rutin against Cisplatin-Induced Nephrotoxicity in Rats

Objective: To study the nephroprotector activity of the bioflavonoid, rutin (50 and 100 mg/kg, p.o.) on cisplatininduced nephrotoxicity (6mg/kg, i.p.) in albino rats. Materials and Methods: Nephroprotector activity of rutin was assessed by estimating the levels of blood urea nitrogen, serum creatinine, serum total proteins, urinary protein, creatinine clearance, urine to serum creatinine ratio and lipid peroxidation in kidney. Results: Cisplatin elevated the serum markers level, increased the protein excretion in urine, reduced the creatinine clearance, urine to serum creatinine ratio and renal malondialdehyde level was increased. Animals which received rutin, in curative and prophylactic groups significantly reversed the effects induced by cisplatin. Conclusion: From the results it is revealed that rutin effectively reduced the cisplatin-induced renal toxicity in albino rats.

Investigation of cytotoxic, apoptosis-inducing, genotoxic and protective effects of the flavonoid rutin in HTC hepatic cells

Rutin is a flavonoid with antioxidant, vasodilatory, anti-inflammatory and immune-stimulating activities. To study the toxicity of rutin and its protective effect, this work investigated the cytotoxic, apoptosis-inducing, genotoxic and protective effects of rutin in HTC cells. In the MTT assay, the highest concentration tested (810 μM) showed cytotoxicity after 72 h of treatment, where cell viability and cell proliferation was diminished. None of the concentrations of rutin tested induced apoptosis after 24 h treatment. The highest concentration of rutin after 24 h treatment induced DNA damage, shown in the comet assay, but did have a genotoxic effect in the micronucleus test. Rutin was tested against the pro-carcinogenic agent benzo(a)pyrene, at concentrations of 90, 270 and 810 μM, and was found to reduce induced DNA damage significantly. This protective effect of rutin against a pro-carcinogen, suggests an important biological activity for this compound, which can contribute to human health through the diet.

Protective effect of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins in streptozotocin-induced diabetic rats

The protective role of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins in streptozotocin-induced diabetic rats has been studied. A single intraperitoneal injection of streptozotocin (50 mg kg(-1)) to rats led to a significant (P < 0.05) increase in the levels of lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in plasma and tissues (liver, kidney, heart and brain). The levels of low density and very low density lipoprotein (LDL and VLDL, respectively) cholesterol were increased, whereas the levels of high density lipoprotein (HDL) cholesterol were decreased significantly (P < 0.05) in plasma. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly (P < 0.05) in liver, kidney and heart, and the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT) decreased significantly (P < 0.05) in the plasma of diabetic rats. Streptozotocin injection also increased the levels of glycoproteins such as hexose, hexosamine, fucose and sialic acid in plasma, liver and kidney. Oral administration of rutin to streptozotocin-induced diabetic rats significantly (P < 0.05) decreased the levels of lipids in plasma and tissues. The levels of plasma HDL-cholesterol increased and the levels of LDL- and VLDL-cholesterol decreased significantly (P < 0.05). The activity of HMG CoA reductase decreased in the tissues and the activity of plasma LPL and LCAT increased significantly (P < 0.05). The levels of glycoproteins were found to be significantly (P < 0.05) decreased in plasma, liver and kidney of rutin-treated diabetic rats. Rutin administration to normal rats did not exhibit any significant (P < 0.05) changes in any of the parameters studied. In conclusion, the beneficial effect of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins could be due to its antioxidant property.

Evaluation of Launaea procumbens use in renal disorders: A rat model

Introduction Carbon tetrachloride exerts its toxicity in rat kidneys through oxidative stress. Launaea procumbens is used ethnopharmacologically in renal disorders. Its methanolic, chloroform, ethyl acetate, and n-hexane fractions were evaluated against CCl 4-induced nephrotoxicity in rat. Materials and Methods Among 16 groups, one was given CCl 4 of 3 ml/kg body weight (30% in olive oil i.p.) twice a week for 4 weeks. Others were orally fed with extracts (100, 200 mg/kg b.w.) or rutin (50 mg/kg b.w.) after 48 h of CCl 4 or 200 mg/kg b.w. of extracts without CCl 4-treatment twice a week for 4 weeks. Results CCl 4 exposure led to a significant oxidative stress in kidneys which was remarkably attenuated with co-administration of various fractions and rutin thereby increased the level of CAT, POD, SOD, GSH, GSR, GST, GSH-Px, quinone reductase, while reduced the xanthine oxidase, γ-GT, TBARS, H 2O 2, nitrite, tissue proteins and DNA fragmentation%. Ameliorated effects of fractions and rutin were also recorded for the function of kidneys and the level of urobilinogen, urea, albumin, creatinine, RBC and WBC in urine were decreased. Serum level of creatinine, urobilinogen, BUN, direct bilirubin, total bilirubin and globulin were decreased while total proteins, albumin and creatinine clearance were increased with fractions and rutin. Protective effects of rutin and fractions were also evident on histopathology by reducing glomerular atrophy, tubular degeneration, congestion of blood capillaries, necrosis of epithelium and edema. Similarly body weight was increased while kidney and relative kidney weight was decreased with co-administration of fractions and rutin. Conclusion It is suggested that Launaea procumbens effectively protect kidneys against the CCl 4-induced oxidative damage in rats, through antioxidant and free radical scavenging effects of flavonoids and saponins present in the fractions.

Rutin inhibits hydrogen peroxide-induced apoptosis through regulating reactive oxygen species mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells

Apoptosis of human vein endothelium cell caused by reactive oxygen species is implicated in the pathogenesis of cardiovascular diseases. Rutin, an active flavonoid compound, is well known to possess potent antioxidant properties against oxidative stress insults through undefined mechanism(s). In this study, we first investigated the possible protective effects of rutin against apoptosis of human umbilical vein endothelial cells (HUVECs) induced by hydrogen peroxide (H 2O 2) and the associated signaling pathways. Decreased viability and increased apoptosis were observed in the HUVECs incubated with 200 μM H 2O 2 for 12 h. By examining the effect of rutin on H 2O 2-induced apoptosis in HUVECs, we found that rutin pretreatment significantly attenuated H 2O 2-induced apoptosis in HUVECs. We next examined the signaling involved in rutin-mediated anti-apoptotic effects. It was found that rutin pretreatment attenuated excessive reactive oxygen species in HUVECs exposed to H 2O 2. Rutin also prevented the increased DNA fragment formation and glutathione (GSH) depletion and inhibited the collapse of mitochondrial membrane potentials (ΔΨm) that occurred in HUVECs exposed to H 2O 2, which protected HUVECs against oxidative damage and the further mitochondrial membrane integrity impairment, leading to apoptosis. In conclusion, the results suggested that rutin (50 µM) blocked apoptosis in HUVECs through decreasing reactive oxygen species, increasing GSH, restoring ΔΨm and thus protecting DNA damage. Our research indicated that rutin protected the intracellular GSH antioxidant system and prevented H 2O 2-induced apoptosis of HUVECs through regulating reactive oxygen species mediated mitochondrial dysfunction pathway.

Influence of rutin treatment on biochemical alterations in experimental diabetes

Dietary antioxidant compounds such as flavonoids may offer some protection against early-stage diabetes mellitus and its complications. Abnormalities in both glucose metabolism and lipid profile constitute one of the most common complications in diabetes mellitus. The present study aimed to evaluate the effect of rutin, through biochemical parameters, on experimental streptozotocin (STZ)-induced diabetes in rats. Male Wistar rats were divided into four groups: untreated controls (GI); normal rats receiving rutin (GII); untreated diabetics (GIII); diabetic rats receiving rutin (GIV). STZ was injected at a single dose of 60 mg kg -1 to induce diabetes mellitus. The diabetes resulted in increased serum glucose, cholesterol, triacylglycerols and lipoproteins (LDL and VLDL-cholesterol) but decresed serum HDL-cholesterol and insulin. Rutin (50 mg kg –1) reduced ( p < 0.05) blood glucose and improved the lipid profile in STZ-induced diabetic rats. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities were significantly augmented in serum of STZ-diabetic rats, while these activities were diminished in hepatic and cardiac tissues compared with the control group. Rutin prevents changes in the activities of ALT, AST and LDH in the serum, liver and heart, indicating the protective effect of rutin against the hepatic and cardiac toxicity caused by STZ. Rutin was associated with markedly decreased hepatic and cardiac levels of tryacylglycerols and elevated glycogen. These results suggest that rutin can improve hyperglycemia and dyslipidemia while inhibiting the progression of liver and heart dysfunction in STZ-induced diabetic rats.

Protective effects of quercetin-3-rhamnoglucoside (rutin) on ischemia-reperfusion injury in rat small intestine

Quercetin-3-rhamnoglucoside (rutin) has a wide spectrum of biochemical and pharmacological activities. Orally administered compounds are absorbed in the intestine. Although absorption of rutin from the jejunum of the rat was good, binding of rutin to the intestinal wall components may limit its absorption from the small intestine. The physiological importance of an orally administered compound depends on its interaction with target tissues. Since there is limited information on the importance of rutin in vivo, we focused on the protective effect of rutin on intestinal injury. The intestinal mucosa is extremely sensitive to reactive oxygen species. We used a rat mesenteric ischemia-reperfusion (I/R) injury model as a model of oxidative injury and investigated the antioxidant activities of rutin in vivo. We found that rutin, which has combined antioxidant activity from radical-scavenging, xanthine oxidase inhibition and chain-breaking effects, exhibits a protective effect on I/R injury in the rat small intestine.

Protective Effect of Rutin on the Ischemia/Reperfusion Induced Damage in Rat Kidney

Reactive oxygen species (ROS) are suggested to participate in ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effect of rutin, a bioflavonoid, in I/R induced renal injury. Wistar albino rats were unilaterally nephrectomized, and 2 wk later they were subjected to 45 min of left renal pedicle occlusion followed by 3h of reperfusion. Either rutin (1g/kg) or saline was administrated (i.p.) 1h prior to ischemia. At the end of the reperfusion period, kidney samples were taken for determination of renal malondialdehyde (MDA) and glutathione (GSH) levels, manganese-superoxide dismutase (MnSOD) activity and histological examination. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level and MnSOD activity, which was accompanied by a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH were elevated in the I/R group compared with the control group. Pretreatment of rats with rutin (1g/kg/ i.p.) significantly attenuated renal dysfunction, reduced elevated MDA levels, and restored the depleted MnSOD activity and GSH levels. These beneficial changes in the biochemical parameters were also associated with parallel changes in histopathological appearance. These findings suggest that ROS play a causal role in I/R induced renal injury, and that rutin exerts renal-protective effects, probably by inhibiting ROS and antioxidant activities.

Rutin from Lonicera japonica inhibits myocardial ischemia/reperfusion-induced apoptosis in vivo and protects H9c2 cells against hydrogen peroxide-mediated injury via ERK1/2 and PI3K/Akt signals in vitro

We investigated pharmacological effects of rutin isolated form Lonicera japonica on H 2O 2-induced cell death in H9c2 cells in vitro and rat myocardial ischemia-reperfusion injury model in vivo. Western blot analysis showed that H 2O 2 increased expression of cleaved form of caspase-3 and proapoptotic Bax protein, but decreased antiapoptotic Bcl-2 protein in H9c2 cell. However, treatment with rutin decreased expression of both cleaved from of caspase-3 and increased Bcl-2/Bax ratio in H9c2 cells. The protective effect of rutin was inhibited not by JNK inhibitor or p38 MAPK inhibitor but by PI3K inhibitor or ERK inhibitor. Rutin increased phosphorylation of ERK and Akt in H9c2 cells. These anti-apoptotic effects of rutin were confirmed both by annexin-V and TUNEL assay. Furthermore, rutin improved I/R-induced myocardial contractile function and reduced infarct size. Rutin administration also inhibited apoptosis in myocardial tissues in I/R rats by increasing Bcl-2/bax ratio and decreasing active caspase-3 expression. These results suggest that rutin reduced oxidative stress-mediated myocardial damage in vitro model and in vivo model, which might be useful in treatment of myocardial infarction.

Protective effect of rutin against spatial memory impairment induced by trimethyltin in rats

Rutin is a flavonoid with various biological activities that are beneficial to human health. Trimethyltin is a toxic organotin compound, and rats injected with trimethyltin serve as a useful in vivo model for studying spatial memory impairment and neurodegeneration in the hippocampus. The protective effect of rutin against the trimethyltin-induced spatial memory impairment and hippocampal neuron damage in rats was examined. Peroral administration of a single dose of trimethyltin (8.5 mg/kg) induced spatial memory loss and the extensive loss of CA3 pyramidal neurons in hippocampi, as indicated by the results of a Morris water maze task and histologic examination, respectively. Prolonged supplementation of rutin significantly reversed the trimethyltin-induced spatial memory impairment and the damage to pyramidal neurons in the hippocampal CA3b region, indicating an antioxidative effect of rutin. These results suggest that rutin in the diet may provide a protective effect against spatial memory impairment accompanied by hippocampal pyramidal neuron loss.

Protective effect of rutin, a polyphenolic flavonoid against haloperidol‐induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes

The occurrence and irreversibility of tardive dyskinesia (TD), a motor disorder of the orofacial region, resulting from chronic neuroleptic treatment has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism underlying the pathophysiology of TD is not completely known. Several animal studies have demonstrated an enhancement of oxidative damage and increased glutamatergic transmission after chronic administration of neuroleptics. The present study investigated the effect of rutin, an antioxidant in haloperidol-induced orofacial dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypic rearing, locomotor activity, percent retention), biochemical [lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase)] and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements, tongue protrusions and facial jerking in rats, which were significantly inhibited by rutin. Chronic administration of haloperidol also resulted in dopamine receptor sensitivity as evident by a well-shaped response (initial decrease followed by increase) in locomotor activity and stereotypic rearing and also decreased percent retention time on elevated plus maze paradigm. Pretreatment with rutin reversed these behavioural changes. Besides, haloperidol also induced oxidative damage in all regions of brain which was prevented by rutin, especially in the subcortical region containing striatum. Although turnover of dopamine and noradrenaline decreased in both cortical and subcortical regions after chronic administration of haloperidol, it was significantly reversed by high-dose rutin treatment. The findings of the present study suggested the involvement of free radicals in the development of neuroleptic-induced orofacial dyskinesia, a putative model of TD, and rutin as a possible therapeutic option to treat this hyperkinetic movement disorder.

Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury

The present study is designed to investigate the effect of dietary flavanoid rutin, micronutrient selenium and garlic oil on ischaemia and reperfusion-induced cerebral injury. Global cerebral ischaemia was induced by occluding right and left common carotid arteries for 10 min followed by reperfusion for 24 h. Cerebral infarct size was estimated using triphenyltetrazolium chloride staining. Elevated plus maze was employed to estimate short-term memory. Degree of motor incoordination was evaluated using inclined beam-walking test and lateral push test. Mitochondrial thiobarbituric acid reactive substances (TBARS) assay was employed as an index of oxidative stress. Global cerebral ischaemia followed by reperfusion produced a significant impairment in short-term memory and motor coordination and produced a notable increase in mitochondrial TBARS. Administration of rutin and garlic oil before global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. Administration of sodium selenite either before or after global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. The protective effect of rutin, sodium selenite and garlic oil was accompanied by a marked decrease in mitochondrial TBARS. On the basis of these results, it may be suggested that rutin and garlic oil administrated before cerebral ischaemia may scavenge reactive oxygen species and consequently attenuate global cerebral ischaemia and reperfusion-induced cerebral injury. Sodium selenite administrated before and after cerebral ischaemia may be neuroprotective due to its antioxidant effect.

Protective effect of rutin on paracetamol- and CCl 4-induced hepatotoxicity in rodents

Rutin, a well-known flavonoid was investigated for its possible protective effect against paracetamol- and CCl 4-induced hepatic damage. Paracetamol produced 100% mortality at the dose of 1 g/kg in mice while pre-treatment of animals with rutin (20 mg/kg) reduced the death rate to 40%. Oral administration of a sub-lethal dose of paracetamol (640 mg/kg) produced liver damage in rats as manifested by the rise in serum level of transaminases (AST and ALT). Pre-treatment of rats with rutin (20 mg/kg) prevented the paracetamol-induced rise in serum enzymes. The hepatotoxic dose of CCl 4 (1.5 ml/kg; orally) also raised the serum AST and ALT levels. The same dose of rutin (20 mg/kg) was able to prevent the CCl 4-induced rise in serum enzymes. Rutin also prevented the CCl 4-induced prolongation in pentobarbital sleeping time confirming its hepatoprotectivity. These results indicate that rutin possesses hepatoprotective activity and the presence of this compound in Artemisia scoparia may explain the folkloric use of the plant in liver damage.

Influence of Metal Ions on Flavonoid Protection against Asbestos-Induced Cell Injury

Influence of metal ions (Fe2+, Fe3+, Cu2+, Zn2+) on the protective effect of rutin, dihydroquercetin, and green tea epicatechins against in vitro asbestos-induced cell injury was studied. Metals have been found to increase the capacity of rutin and dihydroquercetin to protect peritoneal macrophages against chrysotile asbestos-induced injury. The data presented here show that this effect is due to the formation of flavonoid metal complexes, which turned out to be more effective radical scavengers than uncomplexed flavonoids. At the same time epicatechins and their metal complexes have similar antiradical properties and protective capacities against the asbestos induced injury of macrophages. Metal complexes of all flavonoids were found to be considerably more potent than parent flavonoids in protecting red blood cells against asbestos-induced injury. It was also found that the metal complexes of all flavonoids were absorbed by chrysotile asbestos fibers considerably better than uncomplexed compounds and probably for this reason flavonoid metal complexes have better protective properties against asbestos induced hemolysis. Thus, the results of the present study show that flavonoid metal complexes may be effective therapy for the inflammatory response associated with the inhalation of asbestos fiber. The advantage of their application could be the strong increase in ROS scavenging by flavonoids and finally a better cell protection under the conditions of cellular oxidative stress.

Protective effect of rutin, a flavonol glycoside, on the carcinogen-induced DNA damage and repair enzymes in rats.

Administration of hepatocarcinogens aflatoxin B1 and N-nitrosodimethylamine to rats caused single-strand breaks in nuclear DNA. Inclusion in the diet of rutin, a naturally occurring phenolic flavonoid glycoside, significantly reduced the appearance of such breaks. The protection against DNA damage was found to be reduction in the induction of repair enzymes polymerase, DNA polymerase beta and DNA ligase. Even associated with poly(ADP-ribose) a marginal dose of rutin was effective in this regard. Since DNA damage and inefficient repair are expected to initiate the process of carcinogenesis, modulation by rutin of these parameters emphasizes the protective role of this flavonoid against carcinogenesis induced by chemical carcinogens.

Protective effects of rutin against hemoglobin oxidation

A prooxidant drug, primaquine (PQ) was used to produce oxidative stress in human red blood cells (RBC) vitro. Rutin, a plant flavonoid, did not prevent PQ-induced cell lysis but protected against hemoglobin (Hb) oxidation inside RBC. After PQ removal, rutin failed to reduce preformed met-Hb indicating that the rutin protective effect manifests only in the presence of PQ. Since H 2O 2; was proved to mediate PQ-induced Hb oxidation, authentic Hb was studied for its reaction with H 2O 2; and rutin in solution. Rutin partially protected oxy-Hb against H 2O 2-induced oxidation and heme loss. Rutin was also shown to delay H 2O 2-induced met-Hb oxidation to ferryl-Hb. Rutin directly reduced ferryl-Hb to met-Hb in stoichiometric (1:1) reaction characterized by a rate constant of 100 to 130/M/sec. It is assumed that by reducing ferryl-Hb, rutin prevents oxy-Hb from reacting with ferryl-Hb (comproportionation reaction), thus preventing half of the oxy-Hb molecules from being converted to met-Hb. This mechanism is consistent with 50% inhibition by rutin (at the maximum of its activity) of PQ-induced oxy-Hb oxidation in RBC. The present results demonstrate new antioxidant properties of rutin that may be useful in diminishing oxidative damage to pathological red blood cells.