Renal Antioxidant Enzyme Activities Research Articles

Therapeutic Efficacy of Natural Product 'C-Phycocyanin' in Alleviating Streptozotocin-Induced Diabetes via the Inhibition of Glycation Reaction in Rats.

Diabetes is a long-term metabolic disorder characterized by persistently elevated blood sugar levels. Chronic hyperglycemia enhances glucose-protein interactions, leading to the formation of advanced glycation end products (AGEs), which form irreversible cross-links with a wide variety of macromolecules, and accumulate rapidly in the body tissues. Thus, the objective of this study was to assess the therapeutic properties of C-phycocyanin (C-PC) obtained from Plectonema species against oxidative stress, glycation, and type 2 diabetes mellitus (T2DM) in a streptozotocin (STZ)-induced diabetic Wistar rat. Forty-five days of C-PC administration decreased levels of triglycerides (TGs), blood glucose, glycosylated hemoglobin, (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), liver and kidney function indices, and raised body weight in diabetic rats. C-PC suppressed biochemical glycation markers, as well as serum carboxymethyllysine (CML) and fluorescent AGEs. Additionally, C-PC maintained the redox state by lowering lipid peroxidation and protein-bound carbonyl content (CC), enhancing the activity of high-density lipoprotein cholesterol (HDL-C) and renal antioxidant enzymes, and preserving retinal and renal histopathological characteristics. Thus, we infer that C-PC possesses antidiabetic and antiglycation effects in diabetic rats. C-PC may also act as an antidiabetic and antiglycation agent in vivo that may reduce the risk of secondary diabetic complications.

Effects of Fructose and Stress on Rat Renal Copper Metabolism and Antioxidant Enzymes Function.

The effects of a fructose-rich diet and chronic stress on copper metabolism in the kidneys are still understudied. We investigated whether fructose and/or chronic unpredictable stress modulate copper metabolism in a way that affects redox homeostasis, thus contributing to progression of metabolic disturbances in the kidney. We determined protein level of copper transporters, chaperones, and cuproenzymes including cytochrome c oxidase, as well as antioxidant enzymes function in the kidneys of male Wistar rats subjected to 20% liquid fructose supplementation and/or chronic stress. Liquid fructose supplementation increased level of copper chaperone of superoxide dismutase and decreased metallothionein level, while rendering the level of copper importer and copper chaperones involved in copper delivery to mitochondria and trans Golgi network unaffected. Stress had no effect on renal copper metabolism. The activity and expression of renal antioxidant enzymes remained unaltered in all experimental groups. In conclusion, fructose, independently of stress, decreased renal copper level, and modulated renal copper metabolism as to preserve vital cellular function including mitochondrial energy production and antioxidative defense, at the expense of intracellular copper storage.

Polydatin-loaded chitosan nanoparticles ameliorates early diabetic nephropathy by attenuating oxidative stress and inflammatory responses in streptozotocin-induced diabetic rat.

In various developed countries, diabetic nephropathy (DN) is the principal cause of end-stage kidney disease and a main reason of injury and mortality in individuals with renal morbidity worldwide. Polydatin (POL) has been evaluated as a potential antioxidant, anti-inflammatory and a nephroprotective agent. In spite of this, the possible benefits and protective effects of POL on early diabetic nephropathy are not quite clarified. For the effective clearance from the body besides safe drug delivery, biodegradable nanoparticles have interesting attraction. This work was designed to evaluate the positive effect and possible mechanisms of Polydatin-loaded Chitosan-Nanoparticles (POL-NPs) on early DN in streptozotocin-induced diabetic rats. Followed the induction of diabetes, rats classified into four groups, diabetic control and diabetic rats treated daily and orally with; POL, Polydatin-loaded chitosan-Nanoparticles (POL-NPs), plus normal control rats. Our findings showed that diabetic group presented a significant high level of the blood glucose, blood glycosylated hemoglobin (HbA1c), serum insulin, renal function related parameters, renal Advanced glycation-end products (AGEs) and lipid peroxidation level compared to normal control rats, while serum albumin level and the activities of renal antioxidant enzymes were significantly decreased. Moreover, in the kidney of diabetic rat mRNA expression of nuclear factor-kappa B (NF-κB) and cyclooxygenase-2 (Cox-2) were up-regulated. Besides, increase in serum levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-18) and decrease in anti-inflammatory cytokine (IL-10). POL and POL-NPs supplementation were significantly attenuate the above-mention results and returned the normal equilibrium between pro- and anti-inflammatory cytokines. In conclusion, POL and POL-NPs have antidiabetic effect, suppresses oxidative stress and mitigates renal inflammation through inhibition of NF-κB in diabetic kidney in early progressive DN.

Protective effects of Vitex pseudo-negundo leaves on diabetic-induced nephropathy in rats.

Objectives The belief of therapeutic effects of herbal remedies in diseases such as diabetes is rooted in medical history. The present study evaluated protective efficacy of the hydroalcoholic extract of Vitex pseudo-negundo leaves (VLHE) on the renal disorders in streptozotocin-induced diabetic rats. Methods Fifty Wistar male rats were recruited and divided into five groups of 10, including healthy controls and diabetic controls: three diabetic groups of which first group was treated with glibenclamide, and two groups treated with 250 and 500mg/kg of VLHE, respectively, for six weeks. Renal biochemical tests and tissue histopathological evaluation were performed and the antioxidant status was examined. Results There were significant decreases in superoxide dismutase and glutathione peroxidase activities and increases in malondialdehyde levels in renal tissue of diabetic groups compared with healthy controls. In the VLHE-treated rats, fasting blood sugar, blood urea nitrogen and creatinine were declined, serum albumin elevated, kidney weight lowered, lipid peroxidation and reinforcement of the activities of antioxidant enzymes decreased compared with healthy groups. Histological assessments revealed that the vacuolar degeneration of tubules and shrinkage of glomeruli in VLHE-treated rats was decreased compared with diabetic rats. Conclusions The study suggested that administrating of VLHE in nephropathic rats ameliorated the disease by reduction of oxidative stress and increase in renal antioxidant enzyme activities.

Renal changes and apoptosis caused by subacute exposure to Aroclor 1254 in selenium-deficient and selenium-supplemented rats.

Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls, exerts hepatic, renal, and reproductive toxicity in rodents. This study aimed to determine a protective role of selenium on histopathological changes, oxidative stress, and apoptosis caused by A1254 in rat kidney. It included a control group, which received regular diet containing 0.15 mg/kg Se (C), a Se-supplemented group (SeS) receiving 1 mg/kg Se, a Se-deficient group (SeD) receiving Se-deficient diet of ≤0.05 mg/kg Se, an A1254-treated group (A) receiving 10 mg/kg of Aroclor 1254 and regular diet, an A1254-treated group receiving Se-supplementation (ASeS), and an A1254-treated group receiving Se-deficient diet (ASeD). Treatments lasted 15 days. After 24 h of the last dose of A1254, the animals were decapitated under anaesthesia and their renal antioxidant enzyme activities, lipid peroxidation (LP), glutathione, protein oxidation, and total antioxidant capacity levels measured. Histopathological changes were evaluated by light and electron microscopy. Apoptosis was detected with the TUNEL assay. Kidney weights, CAT activities, and GSH levels decreased significantly in all A1254-treated groups. Renal atrophic changes and higher apoptotic cell counts were observed in the A and ASeD groups. Both groups also showed a significant drop in GPx1 activities (A – 34.92 % and ASeD – 86.46 %) and rise in LP (A – 30.45 % and ASeD – 20.44 %) vs control. In contrast, LP levels and apoptotic cell counts were significantly lower in the ASeS group vs the A group. Histopathological changes and renal apoptosis were particularly visible in the ASeD group. Our findings suggest that selenium supplementation provides partial protection against renal toxicity of Aroclor 1254.

Nephroprotective Effect of Moringa Oleifera Seed Oil on Gentamicin-Induced Nephrotoxicity in Rats: Biochemical Evaluation of Antioxidant, Anti-inflammatory, and Antiapoptotic Pathways

Objective: Gentamicin is an efficacious aminoglycoside antibiotic widely used to treat life-threatening Gram-negative bacteria infections. However, its specific non-targeted induction of nephrotoxicity is a worrying clinical challenge. The study explored the nephroprotective effect of Moringa oleifera seed oil (MOO) against gentamicin-induced oxidative nephrotoxicity, pro-inflammation, and apoptosis in male Wistar rats. Method: Twenty-four rats divided into 4 groups (n = 6) were administered MOO (5 ml/kg) for 16 days and/or gentamicin (100 mg/kg bw/d, ip) injected from day 11 to day 16. The renal antioxidant enzyme activities reduced glutathione, lipid peroxidation, and serum renal markers. Urea and creatinine levels were estimated. The renal expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) were determined. Renal levels of inducible nitric oxide synthase (iNOS), nuclear factor-ĸB (NF-ĸB), and caspase-3 were determined to detect possible mechanism of inflammation and apoptosis with histology. Results: MOO prominently reduced serum creatinine and urea levels with amelioration of histopathological abrasions induced by gentamicin (GM). It significantly depressed oxidative stress through lowering of renal malondialdehyde (MDA) and elevation of renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) level. MOO restored renal content of IL-1β, IL-6, TNF-α, and NO, coupled with the mechanistic downregulation of NF-ĸB, iNOS, and caspase-3 activities. The histopathological alterations were ameliorated by MOO. Conclusions: MOO possesses marked nephroprotective effect against GM-induced renal damage via modulating oxidative stress, inflammation, and apoptosis in Wistar rats.

Has vitamin E any shreds of evidence in cisplatin-induced toxicity.

Cisplatin is one of the highly consumed and effective antitumor agents whose clinical application is accompanied by nephrotoxicity adverse reaction. Also, other complications such as ototoxicity and hepatotoxicity are a matter of concern. Today, it is suggested that cisplatin-associated toxicities are mainly induced by free radicals production, which will result in oxidative organ injury. The evidence is growing over the protective effects of antioxidants on cisplatin-induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin-induced nephrotoxicity and ototoxicity are reviewed here at the light of pertinent results from basic and clinical research. Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decreasing the level of malondialdehyde, reducing serum urea and creatinine, and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione-S-transferase, and superoxide dismutase. Although the data from most of the studies are in favors of protective effects of vitamin E against cisplatin-induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.

Taurine Ameliorates Thyroid Hypofunction and Renal Injury in L-NAME-Induced Hypertensive Rats.

There is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, L-NAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

Comparative study of radioprotective effects of selenium nanoparticles and sodium selenite in irradiation-induced nephropathy of mice model

Purpose: The current study was undertaken to evaluate radioprotective effects of selenium (Se) nanoparticles in irradiation-induced nephropathy of mice model compared to sodium selenite.Materials and methods: Forty-five mice were divided into three major groups including control, Se nanoparticle, and sodium selenite. Each major group was further subdivided into three more groups receiving various doses of 0, 2, and 8 Gy gamma irradiation. Both of the supplements were administered intraperitoneally with the dose of 0.1 mg/kg for 14 consecutive days. At the end of each week, the animals were exposed to gamma radiation and 48 h after the last exposure, the animals were humanely euthanized, then blood and renal tissue samples were taken. Serum creatinine, urea, cystatin C, and beta-2-microglobulin levels as well as activities of renal antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase, also malondialdehyde level, total antioxidant capacity, renal tissue Se content, and histopathological features were assessed.Results: The results showed that both of the supplements could normalize aforementioned indices. However, selenium nanoparticles (Se-NPs) were more effective than sodium selenite.Conclusions: Conclusively, Se-NPs as an emerging potent antioxidant agent can protect against irradiation-induced nephropathy.

Antioxidant and Nephroprotective Potential of Aegle marmelos Leaves Extract

ABSTRACTThe nephroprotective activity of hydro-alcoholic (HAEAM) and ethyl acetate (EAEAM) extracts of Aegle marmelos leaves were evaluated against nephrotoxicity induced by cisplatin (CP), a widely used chemotherapeutic agent in cancer therapy. Wistar rats were treated with CP (6 mg.kg–1; i.p.). Treatment groups received the same dose of CP, along with HAEAM and EAEAM (200 and 400 mg.kg–1) orally for 5 d. Blood urea nitrogen (BUN), serum creatinine, and antioxidant enzymes were estimated in renal tissues. EAEAM exhibited minimum IC50 values 6.13 ± 1.05, 67.34 ± 1.7, 59.7 ± 3.9, and 49.17 ± 2.19 μg.mL–1. EAEAM (400 mg.kg–1) decreased the creatinine levels from 2.29 ± 0.387 to 0.96 ± 0.095 mg.dL–1 and BUN from 92.06 ± 7.949 to 38.18 ± 5.686 mg.dL–1 and restored the activities of renal antioxidant enzymes, decreased the lipid peroxidasde (LPO) levels from 158.70 ± 3.542 to 106.91 ± 5.876 nM.g–1, and increased superoxide dismutase (SOD) levels from 12.59 ± 0.463 to 29.95 ± 5.222 U.g–1, glutathione (GSH) from 0.24 ± 0.029 to 0.57 ± 0.048 μM.g–1, and catalase (CAT) from 1.14 ± 0.067 to 3.27 ± 0.296 U.mg–1).

Potential protective effects of vitamin E in cisplatin-induced toxicity

Introduction: Cisplatin is one of highly consumed and effective antitumor agents while its clinical application is accompanied by nephrotoxicity adverse reactions. Also other complication such as ototoxicity and hepatotoxicity are matter of concern. Today, it is suggested that cisplatin-induced toxicities are mainly induced by free radical production, leading to oxidative organ injury. Evidences are growing over the protective effects of antioxidants on cisplatin induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin-induced nephrotoxicity and ototoxicity will be reviewed here at the light of pertinent results from basic and clinical researches. Methods: All available in vitro and in vivo studies, clinical trials, and meeting abstracts in English language that examined the protective effects of vitamin E and its derivative in cisplatin-induced toxicity were considered. Materials were obtained by searching ELSEVIER, web of knowledge, PubMed, Scopus, clinical trials, and Cochrane database of systematic reviews. Results: Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decrease in level of malondialdehyde, reduction in serum urea and creatinine and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione-S-transferase and superoxide dismutase. Conclusion: Although the data from most of studies were in favors of protective effects of vitamin E against cisplatin-induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

ABSTRACTObjectives: Arsenic is a ubiquitous element that is widely distributed in the environment to which man and animals are exposed. Cardiovascular disease is one of the aftermaths of chronic arsenic exposure-related morbidity and mortality. This study sought to investigate the possibility of reversal from arsenic-induced cardio-renal toxicity following exposure and subsequent withdrawal. The study also seeks to understand the mechanism of action of this reversal.Methods: Rats were orally exposed to sodium arsenite at 10, 20 and 40 mg/kg daily for 4 weeks followed by 4 weeks of withdrawal.Results: Exposure to arsenic caused a significant increase in malondialdehyde, H2O2 generation but decrease total thiol and reduced glutathione levels in both cardiac and renal tissues. Furthermore, increases in superoxide dismutase, glutathione-S-transferase and catalase with significant increases in glutathione peroxidase activities were observed in the cardiac tissues. On the contrary, a significant reduction in the renal antioxidant enzyme activity was recorded following exposure. Also, antioxidant defense system did not return to apparent values after arsenic withdrawal. Immunohistochemistry revealed a reduction in the expression of the pro-survival protein–protein kinase B (Akt/PKB) following exposure to arsenic and this was not reversed by withdrawalDiscussion: Exposure to arsenic caused cardio-renal toxicity via induction of oxidative stress and down-regulation of Akt/PKB expressions.

Amelioration of Gamma-hexachlorocyclohexane (Lindane) induced renal toxicity by Camellia sinensis in Wistar rats.

Aim:A study to assess the toxic effects of gamma-hexachlorocyclohexane (γ-HCH) (lindane) and ameliorative effects of Camellia sinensis on renal system has been carried out in male Wistar rats.Materials and Methods:Four groups of rats with 18 each were maintained under standard laboratory hygienic conditions and provided feed and water ad libitum. γ-HCH was gavaged at 20 mg/kg b.wt. using olive oil as vehicle to Groups II. C. sinensis at 100 mg/kg b.wt. was administered orally in distilled water to Group IV in addition to γ-HCH 20 mg/kg b.wt. up to 45 days to study ameliorative effects. Groups I and III were treated with distilled water and C. sinensis (100 mg/kg b.wt.), respectively. Six rats from each group were sacrificed at fortnight intervals. Serum was collected for creatinine estimation. The kidney tissues were collected in chilled phosphate buffer saline for antioxidant profile and in also 10% buffered formalin for histopathological studies.Results:γ-HCH treatment significantly increased serum creatinine and significantly reduced the renal antioxidative enzymes catalase, superoxide dismutase, and glutathione peroxidase. Grossly, severe congestion was noticed in the kidneys. Microscopically, kidney revealed glomerular congestion, atrophy, intertubular hemorrhages, degenerative changes in tubular epithelium with vacuolated cytoplasm, desquamation of epithelium and urinary cast formation. A significant reduction in serum creatinine levels, significant improvement in renal antioxidant enzyme activities and near to normal histological appearance of kidneys in Group IV indicated that the green tea ameliorated the effects of γ-HCH, on renal toxicity.Conclusion:This study suggested that C. sinensis extract combined with γ-HCH could enhance antioxidant/detoxification system which consequently reduced the oxidative stress thus potentially reducing γ-HCH toxicity and tissue damage.

NEPHROPROTECTIVE EFFECT OF AQUEOUS EXTRACT OF SOLANUM NIGRUM LINN LEAVES OR SEEDS AND THEIR MIXTURE AGAINST GENTAMICIN-INDUCED NEPHROTOXICITY IN RATS

Abstract The present study aimed to elucidate the nephroprotective effect of different doses of aqueous extract of Solanum Nigrum Linn (AE-SN)leaves or seeds and their mixture against gentamicin-induced nephrotoxicity in rats. Forty eight mature male rats weighted (160±5g) were randomly divided into eight groups 6 rats each. Group (1) rats were fed on basal diet and served as a negative control, while the other 7 groups were intoxicated by a single intraperioneal dose (100 mg/kg) of gentamicin to rats at the 4th week; once daily for end of the experiment (4 weeks) for induction of nephrotoxicity. Group (2) was kept intoxicated ( a positive control group ) while groups 3, 4, 5 and 6 were pre- treated orally with AE-SN extract of leaves and seeds in a dose of 250 and 500mg/kg b.wt., respectively for 4 weeks. Groups 7 and 8 were pre- treated orally with a mixture of aqueous extract of Solanum Nigrum Linn leaves and seeds in a dose of 250 and 500mg/kg b.wt respectively for 4 weeks.Feed intake was calculated daily and body weight gain was recorded weekly. Blood samples were collected and kidneys were weighted, dissected out and taken for biochemical analyses and histopathological study. Pre- treatment with AE-SN extract of leaves or seed and their mixture improved feed intake and increased body weight gain and normalized kidney weight compared to GM intoxicated rats. Also AE-SN significantly improved levels of renalmarkers and maintaining the electrolyte balance by decreasing serum level of some mineral element (Na, K and P), and increase level of calcium and vit. D. in serum compared to negative control group. Improved renal function by AE-SN treatment caused an increase in Renin , Erythropoietin (EPO) and parathyroid hormones. There were also an increase in renal antioxidant enzyme activity and partial amelioration of renal degeneration. In conclusion AE-SN aqueous extract of leave was more effective than aqueous extract of seeds. Pre-treatment with AE-SN mixture at high doses, significantly normalized level of renal markers and antioxidant activities. Ameliorative effects of AE-SN leaves or seeds and their mixture against gentamicin induced nephrotoxicity may be attributed to their antioxidant properties. Key words: nephrotoxicity, SolanumNigrumLinn gentamicin & rat.

LYCOPENE ENHANCES RADICAL REDUCING ABILITY IN VIVO

Lycopene is the most abounding carotenoid in tomato fruits and tomato-based products, and reported to be one of the most potent singlet oxygen quencher among various dietary antioxidants. However, there are no reports on the effect of orally administered lycopene on the radical reducing ability in vivo. The radiofrequency electron paramagnetic resonance (EPR) method is a unique technique by which the in vivo reducing ability of an experimental animal can be studied. In this study, the in vivo changes in the renal reducing ability of rats orally administered lycopene were investigated using a 700 MHz EPR spectrometer equipped with a surface-coil-type resonator. Rats were fed either a control diet or a diet containing lycopene (250 mg lycopene/100 g diet) for two weeks and in vivo EPR measurements were conducted. The renal reducing ability of lycopene treated rats was significantly greater than that of the control. Although lycopene was absolutely accumulated in the kidney by lycopene supplementation, there were no notable changes in renal antioxidant enzyme activities such as superoxide dismutase and glutathione peroxidase and renal I±-tocopherol concentration between two groups. This is the first verification of in vivo antioxidant enhancement via dietary lycopene administration, although we need to clarify the mechanism of in vivo antioxidant enhancement by lycopene.

The Role of Matricaria recutita L. and Asparagus officinalis L. against the Neurotoxicity of Diazinon in Rats

Diazinon (DZN) is an organophosphate insecticide used mainly in agriculture and in sheep dips, and is designed as an irreversible acetylcholine esterase inhibitor [1,2]. It is classified as moderately hazardous class-II organophosphate insecticide [3]. Many systems could be affected by organophosphate intoxication are the immune system, urinary system, reproductive system, pancreas and haematological and biochemical changes [4-8]. In addition, showed that neonatal DZN exposure, at doses below the threshold for cholinesterase inhibition has been lasting effects on emotional responses, with preferential effects on males [9,10]. The microsomal enzymes in the liver oxidize DZN are generating more potent acetylcholinesterase inhibitors, such as diazoxon, hydroxydiazoxon and hydroxydiazinon [11]. Diazinon affects mitochondrial membrane transportation in rat liver [12]. Moreover, it interrupts cytochrome P450 system in human liver [13]. Oxidative stress can also be induced by pesticides, either by the overproduction of free radicals or by alteration in antioxidant defence mechanisms, including detoxification and scavenging enzymes [14]. Oxidative stress has been reported to play an important role in the toxicity of various pesticides, including organochlorines, carbamates and pyrethrods [15,16]. The higher oxidative stress in pesticide sprayers is evidenced by increased concentration of plasma and red blood cell thiobarbituric acid reactive substances (TBARS), changes in antioxidant status, and altered activities of cellular enzymes [17]. Treatment of rats with DZN significantly enhances renal lipid peroxidation, which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase (CAT), glutathione peroxidise, glutathione reductase (GSH-R), glucose- 6-phosphate dehydrogenase, glutathione-s-transferase (GST) and depletion in the level of glutathione reduced (GSH). In blood, normal erythrocyte function depends on the intactness of cell membrane, which is the target for many toxic factors, including pesticides. Erythrocyte GSH together with glutathione peroxidase (GSH-Px), GSH-R, GST, gamma-glutamyl transferase (γ-GT), superoxide dismutase (SOD) and CAT efficiently scavenge toxic free radicals and are partly responsible for protecting against lipid peroxidation due to acute/chronic pesticide exposure [18]. There is a relationship between pesticide exposure and the decrease of antioxidant enzymes [19]. Oxidative stress and genotoxic effects of DZN were documented through the changes in total antioxidant capacity (TAC), reduced GSH and oxidative DNA damage [20]. Exposure to low-level of pesticides is known to produce a variety of biochemical and molecular changes, some of which may be responsible for the adverse biological effects reported in human and experimental studies. Many studies have reported that DZN can induce molecular changes and alter gene expression. Jamshidi et al. have found that administration of DZN to rats at doses of 60 mg/ kg significantly decreased expression of glutamate dehydrogenase, the key enzyme of Langerhans islet for the secretion of insulin, gene 18- hour post-administration [21]. Other studies showed that DZN had affected the expression of neurotrophic factors that coordinate neuronal cell differentiation and brain assembly [22]. In addition, Timofeeva et al. found that persisting effect of developmental DZN cholinergic and serotonergic neurotransmitter systems and gene expression as well as behavioural function [9]. Matricaria recutita L. (family Asteraceae, commonly known as German chamomile) is one of the most widely used and welldocumented medicinal plants in the world [23]. Chamomile is also

Prevention of methotrexate-induced nephrotoxicity by concomitant administration of garlic aqueous extract in rat.

Methotrexate (MTX) has been widely used for treatment of cancer and rheumatoid arthritis, but its use has been limited by its nephrotoxicity. This study was carried out to determine whether garlic exerts a protective effect against MTX-induced nephrotoxicity. Nephrotoxicity was induced in rats after a single i.p. injection of MTX (20 mg/kg). Garlic extract (1 mL/100 g b.w.) was given orally for 7 days before and after MTX administration. Serum samples were collected to evaluate urea, creatinine, sodium, phosphorous, potassium, and calcium. Reduced glutathione, catalase, adenosine deaminase, nitric oxide, and malondialdehyde were measured in renal tissue. Tubular injury was evaluated by histopathological examination. MTX increased urea and creatinine levels and led to imbalances in some electrolytes. It also depleted renal antioxidant enzyme levels and increased malondialdehyde, adenosine deaminase, and nitric oxide levels. Histopathological examination showed glomerular and tubular alterations. Pretreatment with garlic significantly improved renal function and increased renal antioxidant enzyme activities. Furthermore, garlic reduced renal oxidative stress and prevented alterations in renal morphology. Garlic treatment has a reversible biochemical and histological effect upon MTX-induced nephrotoxicity.

English

The aim of the study was to investigate the effects of taurine on biochemical parameters in male Wistar rats co-exposed to chlorpyrifos and lead. Fifty rats were divided into five groups of ten rats each. The distilled water (DW) group received distilled water and the soya oil (SO) group received soya oil (1 ml/kg). Other groups were treated sequentially with taurine (50 mg/kg), chlorpyrifos (4.25 mg/kg, 1/20th LD50) and lead (233.25 mg/kg, 1/20th LD50), and the last group received taurine (50 mg/kg), chlorpyrifos (4.25 mg/kg) and lead (233.25 mg/kg). The treatments were administered once daily by oral gavage. The rats were sacrificed and blood samples were collected after 16 weeks. The serum samples were analyzed for proteins, enzymes, urea and creatinine concentration. The hepatic and renal malondialdehyde concentration and activities of hepatic and renal antioxidant enzymes were evaluated. The results indicated that chronic co-administration of chlorpyrifos (CPF) and lead acetate (LA) induced biochemical alterations in the rats. It is proposed that taurine antioxidant (TA) decreased the alterations in the biochemical parameters partly through its antioxidant, hepatoprotective and nephroprotective properties. It is concluded that taurine is a useful prophylactic agent against biochemical toxicity in individuals that are constantly co-exposed to chlorpyrifos and lead in the environment.   Key words: Taurine, chlorpyrifos, lead, oxidative stress, biochemical effects.

Nephroprotective, Diuretic and Antioxidant Effects of Some Medicinal Herbs in Gentamicin-Nephrotoxic Rats

Aim: To investigate the nephroprotective, diuretic and antioxidant effects of extracts of Petroselinum sativum, Eruca sativa and Curcuma longa herbs in gentamicin (GM)-nephrotoxic rats. Material and Methods: Forty two adult male Sprague Dawley rats were randomly distributed into six equal groups. Group 1 was given sterile saline solution by intraperitoneal (i.p.) injection (negative control). Group 2 (nephrotoxic) was injected with GM (80 mg/kg, i.p.) for 8 days during the last week of the experiment. Groups 3, 4, 5 and 6 were orally pretreated with herbs extracts, alone and in combination, for 6 weeks along with GM during the last week. Blood and urine samples were collected for biochemical analyses. Kidney specimens were taken for estimating oxidant/antioxidant parameters and for histopathology. Results: GM induced nephrotoxicity characterized by biochemical and histopathological alterations, increased lipid peroxidation and reduced activity of antioxidant enzymes in kidney tissues. Aqueous extracts of Petroselinum sativum, Eruca sativa and Curcuma longa herbs caused nephroprotective effect as it decreased in the elevated serum urea, creatinine and alkaline phosphatase (ALP) activity and normalized serum levels of Na+ and K+ electrolytes in GM-intoxicated rats. These extracts also increased the urine volume and urinary excretion of Na+ and K+, ameliorated renal tubular necrosis and increased activities of renal antioxidant enzymes in GM-intoxicated rats. Conclusion: Aqueous extracts of Petroselinum sativum, Eruca sativa and Curcuma longa produce nephroprotective, diuretic and antioxidant effects in GM - nephrotoxic rats. These herbs may be beneficial for patients who suffer from kidney diseases and those on GM therapy.