Comparison of nickel oxide nano and microparticles toxicity in rat liver: molecular, biochemical, and histopathological study.

The unique properties of nickel oxide nanoparticles distinguish it from classical nickel compounds, increasing its use in agriculture, industry, and many industrial areas. The aim of this study is to investigate the possible toxicity of nickel oxide and nickel oxide nanoparticles in the liver. For this purpose, Wistar rats were given nickel oxide and nickel oxide nanoparticles orally, intraperitoneally, and intravenously for 21 days. Liver organ weight, biochemical and hematological parameters, oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, and glutathione S transferase), acetylcholinesterase activities, inflammation levels, apoptotic markers, and histopathological changes were evaluated comparatively. When the data obtained were examined in general, it was observed that nickel oxide nanoparticles caused more hepatotoxicity in liver tissue than nickel oxide in terms of oxidative stress parameters, apoptotic markers, inflammation indicators, and other parameters examined. The results suggest that toxicity induced by both nickel oxide and nickel oxide nanoparticles plays an important role in hepatocyte apoptosis.

The ameliorative effects of quercetin and curcumin against subacute nephrotoxicity of fipronil induced in Wistar rats.

Fipronil is a phenylpyrazole insecticide that is widely used in agricultural, veterinary, and public health fields for controlling a wide variety of insect species and it is an environmentally potent toxic substance. Curcumin and quercetin, which are well-known natural antioxidants, are widely used to prevent the harmful effects of free radicals on biological systems. The present study aimed to determine the potential ameliorative effects of quercetin and/or curcumin on fipronil-induced nephrotoxicity in rats. Curcumin (100 mg/kg of body weight), quercetin (50 mg/kg of body weight), and fipronil (3.88 mg/kg of body weight) were administered to male rats by intragastric gavage for 28 consecutive days. In the present study, body weight, kidney weight, the renal function markers (blood urea nitrogen, creatinine, and uric acid levels) in the blood, antioxidant enzyme activities, and malondialdehyde level as markers of oxidative stress, and histological changes of the renal tissue were evaluated. The levels of serum blood urea nitrogen, creatinine, and uric acid were significantly increased in fipronil-treated animals. Additionally, while superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase activities were decreased in the kidney tissue of rats treated with fipronil, malondialdehyde level was significantly increased. Histopathological analyses showed that the glomerular and tubular injury occurred in the renal tissue of fipronil-treated animals. Also, the supplementation of quercetin and/or curcumin with fipronil significantly improved fipronil-induced alterations in renal function markers, antioxidant enzyme activities, malondialdehyde levels, and histological features of renal tissue.

Methomyl-induced nephrotoxicity and protective effect of curcumin in male rats.

We investigated the ameliorative effect of the curcumin against methomyl-induced potential nephrotoxicity in Wistar albino male rats. In the present study, curcumin (100 mg kg-1 bw), methomyl (0,8 mg kg-1 bw) and methomyl plus curcumin were given to rats by oral for 28 days (for subacute examination). Concentrations of blood urea nitrogen, uric acid and creatinine in serum and malondialdehyde level and activities of antioxidant enzyme (superoxide dismutase, catalase, glutathione peroxidase and glutathione S transferase) and histopathological alterations in kidney tissues were studied. Methomyl caused an increment in the concentrations of blood urea nitrogen, creatinine, uric acid and MDA levels. In addition, methomyl caused a diminution in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S transferase. Tubular and glomerular degenerations occurred in the kidney tissues of methomyl-received rats. However, coadministration of curcumin with methomyl significantly minimized the adverse effects of methomyl on kidney function parameters, lipid peroxidation and antioxidant enzyme activities and histological structure of kidney tissue. The results showed that curcumin significantly mitigated methomyl-induced nephrotoxicity in rats.

Lead nitrate and cadmium chloride induced hepatotoxicity and nephrotoxicity: Protective effects of sesamol on biochemical indices and pathological changes.

Lead nitrate (LN) and cadmium chloride (CdCl2 ), regarded as environmental contaminants, are toxic heavy metals. Sesamol is a dietary phytochemical found in sesame oil. We aimed to analyze the hepatotoxic and nephrotoxic effects of LN and CdCl2 and to evaluate the possible protective effect of sesamol. LN (90 mg/kg bw per day), CdCl2 (3 mg/kg bw per day), and sesamol (50 mg/kg bw per day) were given to rats via gavage for 28 days. Total protein, albumin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total cholesterol, urea, uric acid, creatinine, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, malondialdehyde, acetylcholinesterase, and histopathological changes were investigated in liver and kidney tissues. Lead and cadmium were found to result in decreases in the antioxidant enzymes and acetylcholinesterase activities, increases in malondialdehyde levels, and changes in serum biochemical parameters and various pathological findings. An improvement in all these parameters was observed in the sesamol-treated groups. PRACTICAL APPLICATIONS: Heavy metals are used in many areas of the industry all over the world. Heavy metals which include lead nitrate and cadmium chloride cause cell damage by oxidative stress. Some of the examining parameters for oxidative stress are SOD, GST, MDA, GPx, and CAT. However, some chemicals such as sesamol are well-liked and widely used as antioxidants against xenobiotic toxicity. We also indicate that sesamol has been shown to protective effect against heavy metals caused cell damage.

Bendiocarb-induced nephrotoxicity in rats and the protective role of vitamins C and E.

Bendiocarb is a pesticide carbamate which is used to protect agricultural products and animals. In this study, rats were given orally with bendiocarb and also other chemicals via gavage. Male rats were randomly divided into eight groups (n = 6): group 1 served as controls; group 2 received vitamin C (100 mg/kg bw); group 3 received vitamin E (100 mg/kg bw); group 4 received vitamins C plus E; group 5 received bendiocarb (0.8 mg/kg 1/50 LD50); group 6 received both bendiocarb and vitamin C; group 7 received both bendiocarb and vitamin E; and group 8 received both bendiocarb and vitamin C and E via oral gavage. Degenerative changes and biochemical differences in rat kidney were investigated after 4 weeks of especially bendiocarb treatment. While biochemical values were normal in the control group, it was observed that CAT, SOD, GPx, and GST values decreased, while MDA, creatine, urea, and uric acid values increased in the pesticide-treated groups. It was also reported that bendiocarb caused cytopathological and histopathological changes in rat kidney. We have shown that the application of vitamins has a therapeutic effect on the evaluated parameters.

Testicular toxicity of orally administrated bisphenol A in rats and protective role of taurine and curcumin.

Bisphenol A (BPA) is an endocrine disrupting chemical widely used in the world. Curcumin, the yellow bioactive compound of turmeric has demonstrated its antioxidant activities. Taurine is a low-molecular weight organic compound in living organisms. The present study was aimed to investigate the adverse effects of BPA and its protection by taurine and curcumin. Oral BPA, curcumin and taurine administration in adult male rats at 130mg/kg bw, 100mg/kg bw and 100mg/kg bw, respectively for four weeks. Pathology and oxidative damages were investigated. The results show that BPA increased malondialdehyde (MDA) levels and decreased antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST)] in testes of rats compared to the control group. Co-treatment with curcumin or taurine with BPA led to reduce in MDA and increased GPx, GST, CAT, SOD activities compared to BPA group. Furthermore, while some pathological findings were observed in testis tissues in BPA treated group, less histopathological findings were shown in BPA plus curcumin and/or taurine treated groups. Consequently, curcumin and taurine significantly protect BPA induced testicular damage in rats.

Histopathological and biochemical studies on the effect of curcumin and taurine against bisphenol A toxicity in male rats.

Bisphenol A (BPA) is a chemical found in environmental xenoestrogen. In the present study, olive oil, curcumin, taurine, BPA, curcumin plus BPA, and taurine plus BPA were exposed to rats for 4 weeks via gavage. Content of malondialdehyde and activities of antioxidant enzymes (GPx, GST, SOD, CAT) and also histopathological and cytopathological changes of heart were studied. No significant changes in all studied parameters were seen between control, olive oil, curcumin, and taurine-treated groups. However, there were significant differences in levels of malondialdehyde and activities of antioxidant enzymes in BPA-exposed rats and some histo/cytopathological changes determined. In curcumin plus BPA-exposed and taurine plus BPA-exposed groups, we measured the preventive effects on some parameters but not exactly. As a result, curcumin and taurine significantly minimized BPA-induced cardiotoxicity in rats.

Bendiocarb induced histopathological and biochemical alterations in rat liver and preventive role of vitamins C and E.

In this study, biochemical changes and histological structure of rat liver after bendiocarb administration and possible preventive effects of vitamins C and E were studied. The animals were given with bendiocarb, vitamin C and vitamin E, daily 0,8mg/kg of body weight (bw), 100mg/kg-bw and 100mg/kg-bw for 28days, respectively. Lipid peroxidation, antioxidant enzyme activities, histological alterations and antioxidant capacity assays of liver and also liver function tests and lipid profile were measured. Bendiocarb treatment decreased the antioxidant enzyme activities, FRAP and TEAC values and increased malondialdehyde levels compared to control. Also, there were statistically significant alterations in liver function tests, lipid profile parameters and histopathological changes in bendiocarb treated groups. Vitamins C and E showed protective effects against examining parameters. According to results we can say that co-treatment of vitamin C and vitamin E may be more effective than use of them alone.

Subacute effects of low dose lead nitrate and mercury chloride exposure on kidney of rats.

Lead nitrate and mercury chloride are the most common heavy metal pollutants. In the present study, the effects of lead and mercury induced nephrotoxicity were studied in Wistar rats. Lead nitrate (LN, 45 mg/kg b.w/day) and mercury chloride (MC, 0.02 mg/kg b.w/day) and their combination were administered orally for 28 days. Four groups of rats were used in the study: control, LN, MC and LN plus MC groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in kidney tissues were investigated in all treatment groups. LN and MC caused severe histopathological changes. It was shown that LN, MC and also co-treatment with LN and MC exposure induced significant increase in serum urea, uric acid and creatinine levels. There were also statistically significant changes in antioxidant enzyme activities (SOD, CAT, GPx and GST) and lipid peroxidation (MDA) in all groups except control group. In this study, we showed that MC caused more harmful effects than LN in rats.

Nephrotoxic effects of lead nitrate exposure in diabetic and nondiabetic rats: Involvement of oxidative stress and the protective role of sodium selenite.

Heavy metals are known to be toxic to organisms. The present study was undertaken to evaluate the protective effect of sodium selenite against lead nitrate (LN)-induced nephrotoxicity in diabetic and nondiabetic rats. Animals were divided into eight groups where the first was served as a control, whereas the remaining groups were treated with sodium selenite (1 mg/kg b.w.), LN (22.5 mg/kg b.w.) and a combination of LN and sodium selenite and diabetic forms of these groups. Changes in antioxidant enzyme activities, malondialdehide levels, serum urea, uric acid, creatinine levels, body, and kidney weights and histopathological changes were determined after 28 days. LN caused severe histopathological changes, increment in urea, uric acid, creatinine, and MDA levels, also decreasing in antioxidant enzyme activities, body, and kidney weights. In sodium selenite + LN group, we observed the protective effect of sodium selenite on examining parameters. Also diabetes caused alterations on these parameters compared with nondiabetic animals. We found that sodium selenite did not show protective effect on diabetes caused damages. As a result, LN caused nephrotoxicity and sodium selenite alleviated this toxicity but sodium selenite did not protect kidneys against diabetes mediated toxicity. Also, LN caused more harmfull effects in diabetic groups compared with nondiabetic groups. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1229-1240, 2016.

Protective effects of sodium selenite on lead nitrate-induced hepatotoxicity in diabetic and non-diabetic rats.

In the present study, the effect of sodium selenite on lead induced toxicity was studied in Wistar rats. Sodium selenite and lead nitrate were administered orally for 28 days to streptozotocin induced diabetic and non-diabetic rats. Eight groups of rats were used in the study: control, sodium selenite, lead nitrate, lead nitrate+sodium selenite, streptozotocin-induced diabetic-control, diabetic-sodium selenite, diabetic-lead nitrate, diabetic-lead nitrate+sodium selenite groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in liver tissues were investigated in all groups. There were statistically significant changes in liver function tests, antioxidant enzyme activities and lipid peroxidation levels in lead nitrate and sodium selenite+lead nitrate treated groups, also in diabetic and non-diabetic groups. Furthermore, histopathological alterations were demonstrated in same groups. In the present study we found that sodium selenite treatment did not show completely protective effect on diabetes mellitus caused damages, but diabetic rats are more susceptible to lead toxicity than non-diabetic rats.

Vitamin E and Sodium Selenite Against Mercuric Chloride-Induced Lung Toxicity in the Rats

The aim of the present study was to elucidate the possible protective role of vitamin E and / or sodium selenite on mercuric chloride-induced oxidative stress and histopathological changes in the lung tissue of the rats. Adult male albino Wistar rats were exposed to mercuric chloride (1.0 mg/kg day) for four weeks. Treatment with mercuric chloride led to oxidative stress by enhancing MDA level and also decreasing superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S transferaz (GST) activities. However, mercuric chloride exposure resulted in histopathological changes in the lung tissue in the rats. MDA level and SOD, CAT GPx and GST activities and histopathological changes modulated in concomitantly supplementation of vitamin E (100 mg/kg day) and /or sodium selenite (0.25 mg/kg day) to mercuric chloride-treated groups.

Effects of lead nitrate and sodium selenite on DNA damage and oxidative stress in diabetic and non-diabetic rat erythrocytes and leucocytes.

The adverse effects of lead nitrate (LN) and the preventive role of sodium selenite were investigated in diabetic and non-diabetic rat blood by measuring trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP), malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) also by evaluating DNA damage with comet assay. LN increased the levels of MDA, tail DNA%, mean tail length and tail moment, decreased the enzymes activities, FRAP and TEAC values. In sodium selenite+LN group, we observed the protective effect of sodium selenite on examining parameters. Diabetes caused alterations on these parameters, too. We found that sodium selenite did not protect against diabetes caused damages. As a result, LN caused toxic effects on blood cells and sodium selenite alleviated this toxicity but it did not show preventive effect against diabetes. Also, LN caused more harmfull effects in diabetic groups than non-diabetic groups.

Protective Effects of Sodium Selenite and Vitamin E on Mercuric Chloride-Induced Cardiotoxicity in Male Rats

This study was designed to investigate the protective effects of sodium selenite and/or vitamin E against mercuric chloride-induced cardiotoxicity. Male Wistar rats (n=48, 310±10 g) were administered mercuric chloride (1.0 mg/kg bw), sodium selenite (0.25 mg/kg bw), vitamin E (100 mg/kg bw), sodium selenite plus mercuric chloride, vitamin E plus mercuric chloride and sodium selenite plus vitamin E plus mercuric chloride daily via gavage for four weeks. Malondialdehyde (MDA) level, antioxidant enzyme activities [total superoxide dismutase (SOD), catalase (CAT), total glutathione peroxidase (GPx) and total glutathione-S-transferase (GST)], and histopathological changes in the heart tissue were evaluated. Results showed that mercuric chloride exposure resulted in an increase in the MDA level and a decrease in the SOD, CAT, GPx and GST activities, with respect to the control. Light microscopic investigations revealed that mercuric chloride induced histopathological changes in the heart tissue. A significant decrease in the MDA level and a significant increase in the SOD, CAT, GPx and GST activities were observed on the supplementation of sodium selenite and/or vitamin E to mercuric chloride-treated rats, which showed that, sodium selenite and/or vitamin E significantly reduced mercuric chloride induced cardiotoxicity, but not protected completely.

Lead Nitrate Induced Testicular Toxicity in Diabetic and Non-Diabetic Rats: Protective Role of Sodium Selenite

Among heavy met als, lead is one of the common pollutants found in the environment and biological system. In the present study, streptozotocin-induced diabetic and normal non-diabetic male Wistar rats were given sodium selenite (1.0 mg/kg bw), lead nitrate (22.5 mg/kg bw) and sodium selenite plus lead nitrate (1.0 mg/kg+22.5 mg/kg bw, respectively) through gavage. At the end of 4th week, malondialdehyde (MDA) levels, antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST)], and histopathological changes of testes were investigated compared to the control group. No significant differences were observed between the control and sodium selenite treated groups. However, lead nitrate increased the levels of MDA, SOD, CAT, GPx and GST activities compared with the control group in diabetic and non-diabetic rats. Light microscopic analyses revealed that lead nitrate induced numerous histopathological changes in testis tissues of diabetic and non-diabetic rats. In the diabetic and non-diabetic sodium selenite plus lead nitrate treated groups, there were statistically significantly decreased MDA levels and antioxidant enzymes activities and mild pathological changes. As a result, sodium selenite significantly reduced lead nitrate induced testicular toxicity for both diabetic and non-diabetic rats.

Chlorpyrifos induced hepatotoxic and hematologic changes in rats: the role of quercetin and catechin.

Chlorpyrifos is an organophosphorus insecticide which is widely used throughout in the world and it caused toxic effects on nontarget organisms especially mammalian. In the present study, catechin, quercetin, chlorpyrifos, catechin+chlorpyrifos, quercetin+chlorpyrifos were given to male rats through gavage for 4weeks. Serum total protein, albumin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, trigliceride, total cholesterol levels, hematological changes, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase activities and malondialdehyde content in liver tissues and also histopathological changes of liver were investigated in the rats compared to control group. No significant differences in all investigated parameters were observed between control, catechin and quercetin groups. There were statistically significantly changes in liver function tests, some hematological parameters, antioxidant enzyme activities and malondialdehyde levels in chlorpyrifos treated group compared to control group. In catechin+chlorpyrifos treated group and quercetin+chlorpyrifos treated group we observed the protective effects of catechin and quercetin on examining parameters but not completely. While some histopathological changes detected in liver tissues in chlorpyrifos treated group, less histopathological changes were observed in catechin+chlorpyrifos and quercetin+chlorpyrifos treated groups at the end of the 4thweek. As a result, catechin and quercetin significantly reduce chlorpyrifos induced hepatotoxicity in rats.

Protective effects of catechin and quercetin on antioxidant status, lipid peroxidation and testis-histoarchitecture induced by chlorpyrifos in male rats.

Mature male Wistar rats were given chlorpyrifos (5.4 mg/kg, 1/25 of the oral LD(50)), catechin (20 mg/kg),quercetin (20 mg/kg), catechin plus chlorpyrifos, and quercetin plus chlorpyrifos daily via gavage for four weeks. No statistical differences were found in the catechin-only and quercetin-only groups compared with the control group. By the end of the fourth week, chlorpyrifos alone increased the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), while decreased glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities compared with the control group in rat testis tissues. In the catechin-plus-chlorpyrifos and quercetin-plus-chlorpyrifos groups, there were statistically significantly decreased MDA levels, SOD and CAT activities, while increased GPx and GST activities compared with the chlorpyrifos-only group. Light microscopic analyses revealed that chlorpyrifos-only induced numerous histopathological changes in the testis tissues. Milder pathological alterations were observed in rats catechin-plus-chlorpyrifos, and quercetin-plus-chlorpyrifos. Thus, it appears that catechin and quercetin ameliorate chlorpyrifos induced toxicity except histopathological changes in rat testis tissues.

Dichlorvos-induced testicular toxicity in male rats and the protective role of vitamins C and E.

Dichlorvos is an organophosphorus insecticide that is used worldwide for pest control in agriculture and household use. Vitamins C and E are potential antioxidants protecting cells from oxidative stress. Vitamin C+vitamin E, dichlorvos, a combination of vitamin C+vitamin E+dichlorvos, or corn oil (control) were given to rats via oral gavage for 7 weeks. Body and testis weights, sperm parameters, hormone levels, histo- and cytopathological changes in testes were investigated at the end of 24 h and the 4th and 7th weeks comparatively with the control group. Body and testis weights, sperm morphology, FSH, LH, and testosterone levels were decreased significantly at the end of 4th and 7th weeks in the dichlorvos- and vitamins+dichlorvos-treated groups. A statistically significant decline in sperm motility and testosterone levels occurred by the end of 7th week in the dichlorvos- and vitamins+dichlorvos-treated groups. Light and electron microscopy revealed necrosis, edema and cellular damage in testicular tissues of the dichlorvos- and vitamins+dichlorvos-treated rats at the end of 4th and 7th weeks. In conclusion, dichlorvos caused subacute and subchronic reproductive toxicity, but vitamins did not confer protection.

Protective effects of vitamins C and E against hepatotoxicity induced by methyl parathion in rats.

Male rats were given vitamins C+E, methyl parathion, or both daily via gavage for seven weeks. Body weight was decreased while liver weight increased significantly at the end of fourth and seventh weeks in the methyl parathion- and methyl parathion plus vitamin-treated groups. Serum total protein, albumin, triglyceride, low density lipoprotein-cholesterol (VLDL-cholesterol) levels decreased, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl-transferase (GGT), lactate dehydrogenase (LDH), and total cholesterol levels increased significantly in the methyl parathion- and the methyl parathion plus vitamin-treated rats. There was a statistically significant difference for all biochemical parameters when the methyl parathion plus vitamin-treated group was compared with methyl parathion-treated group. In electron microscopic investigation, cytopathological alterations were observed in hepatocytes of the methyl parathion- and the methyl parathion plus vitamin-treated rats. As a result, methyl parathion-induced hepatotoxicity is reduced by vitamins C+E, but vitamins C+E did not provide complete protection.

Effects of Stevia rebaudiana (Bertoni) extract and N-nitro-L-arginine on renal function and ultrastructure of kidney cells in experimental type 2 Diabetes.

Diabetes is the leading cause of chronic renal failure. Our purpose was to determine the effects of N-nitro-l-arginine (l-NNA) and an extract of Stevia rebaudiana (Bertoni) (SrB) leaves on renal function in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Rats were divided into seven groups. Three of these groups were controls. Diabetes was induced by STZ-NA in the other four. Diabetic rats were treated with SrB (200 mg/kg), L-NNA (100 mg/kg), or SrB + L-NNA for 15 days after 5-8 weeks of diabetes. At the end of the experiments, urine and blood samples were collected from the rats, and kidney tissue samples were collected with the animals under ether anesthesia. Renal filtration changes were determined by measuring urine pH, urine volume, and serum and urine creatinine. Nitric oxide synthase (NOS) activity was measured in kidney homogenates. Alterations in kidney ultrastructure were determined by electron microscopy, and histological changes were examined by hematoxylin and eosin staining. No statistical differences were observed in urine creatinine or creatinine clearance. Even so, we observed higher NOS activity in SrB-treated diabetic rats. SrB-treated diabetic rats had less mitochondrial swelling and vacuolization in thin kidney sections than other diabetic groups. The control groups showed normal histological structure, whereas in the diabetic groups, membrane thickening, tubular epithelial cells, and cellular degeneration were observed. Thus, SrB has beneficial effects on diabetes compared with l-NNA. Our results support the validity of SrB for the management of diabetes as well as diabetes-induced renal disorders.