Protective effects of resveratrol against fumonisin B1-induced liver toxicity in mice.

The aim of this study was to investigate the effects of resveratrol against fumonisin B1 (FB1)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, even though the toxic effects and mechanisms of FB1 and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB1, resveratrol, and FB1+resveratrol groups. Control received saline for 14 days. The FB1 group received 2.25 mg/kg FB1 every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB1+resveratrol group received 2.25 mg/kg FB1 every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB1 group than control. Resveratrol countered FB1 effects for all parameters, including TOS and TAS. Liver histology showed FB1-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB1+resveratrol group. Our findings confirm resveratrol's protective effect against liver damage and oxidative stress caused by FB1. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB1-induced hepatotoxicity.

Boric acid and Borax Supplementation Reduces Weight Gain in Overweight Rats and Alter L-Carnitine and IGF-I Levels.

The aim of this study was to investigate the effects of boric acid (BA) and borax (BX) on live weight and obesity associated molecules including leptin, L-carnitine, insulin-like growth factor 1 (IGF-I), and heat shock proteins 70 (HSP70) in rats fed with high-fat diet. A total of 60 rats were equally allocated as ND (normal diet), HF (high-fat diet), HF+BA, HF+BX, ND+BX, ND+BA. Body weight increases in HF+BA (85 g) and HF+BX (86 g) were significantly lower (p<0.05) compared to HF group (126 g). Boron treatment decreased serum L-carnitine level in high-fat diet (HF+BA 11.12 mg/L, HF+BX 10.51 mg/L, p<0.05) compared to HF group (15.57 mg/L), while no change was observed in groups ND+BA (7.55 mg/L) and ND+BX (7.57 mg/L) compared to group ND (8.29 mg/L). Neither BA nor BX supplementation in ND and HF groups altered the serum levels of HSP70 and leptin. BA and BX supplementation in rats fed HF resulted in a significant reduction in live weight. Boron compounds altered L-carnitine and IGF-1 levels in rats. These results indicate that boron compounds are beneficial in the treatment of obesity as well as in the prevention of high-fat diet-induced weight increase. Alterations in serum L-carnitine and IGF-1 levels in boron treated rats also indicate possible role of boron compounds in energy metabolism in response to high fat diet.

The Therapeutic Role of Glutathione in Oxidative Stress and Oxidative DNA Damage Caused by Hexavalent Chromium.

Hexavalent chromium Cr (VI) causes various toxic and carcinogenic effects. The main carcinogenic effect is observed in the pulmonary system through inhalation route. Reduction of Cr (VI) to Cr (V, IV, and III) reactive intermediates within the cells by intracellular reducing agents such as glutathione is an important event leading to oxidative stress and oxidative DNA damage. This study evaluated the effects of intraperitoneal administration of Cr (VI) and GSH on total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index, and oxidative DNA damage by evaluating the level of 8-hydroxy-2́-deoxyguanosine (8-OHdG) in Swiss-Albino mice. Seventy two mice were divided into 6 groups and treated intraperitoneally as follow: control (saline), group GSH (30 mg/kg GSH) groups of Cr-20 (20 mg/kg, K2Cr2O7), Cr-30 (30 mg/kg K2Cr2O7), Cr-20 + GSH (20 mg/kg K2Cr2O7 + 30 mg/kg GSH), Cr-30 + GSH (30 mg/kg K2Cr2O7 + 30 mg/kg GSH). Total oxidant capacities of Cr-20 and Cr-30 were increased compared to control, Cr-20 + GSH, and Cr-30 + GSH. TOS levels in Cr-20 + GSH and Cr-30 + GSH were lower than in Cr-20 and Cr-30. No difference in TAC was observed among the groups. 8-Hydroxy-2́-deoxyguanosine levels were increased in groups Cr-20 and Cr-30 compared with control and groups Cr-20 + GSH and Cr-30 + GSH. No difference was determined in 8-OHdG levels among control, groups GSH, Cr-20 + GSH and Cr-30 + GSH. Results indicate that Cr (VI) given i.p. route causes increased oxidative stress and oxidative DNA damage in the blood of Swiss-Albino mice. Administration of GSH via i.p. route protects from oxidative stress and DNA damage.

Resveratrol ameliorates cisplatin-induced oxidative injury in New Zealand rabbits.

This study investigated the preventive role of resveratrol in cisplatin-induced nephrotoxicity. The study used groups of New Zealand rabbits that were treated as follows: group C (cisplatin treated), group R (resveratrol treated), group R+C (resveratrol + cisplatin treatment), and group E (control group). Kidney levels of glutathione were significantly lower in group C than in groups E and R, whereas glutathione levels in group R+C were found to be similar to the control values. Malondialdehyde levels in group C were significantly higher than in groups E and R. However, malondialdehyde levels in group R+C were similar to group E. Kidney levels of nitric oxide were significantly higher in the cisplatin group than in the control, whereas nitric oxide levels were at basal values in group R+C. Cisplatin treatment significantly reduced kidney levels of glutathione peroxidase, superoxide dismutase, and catalase activity compared with those of group E, whereas resveratrol treatment significantly increased levels of glutathione peroxidase, superoxide dismutase, and catalase activity in group R+C. However, cisplatin injection did not affect mRNA levels of glutathione peroxidase, superoxide dismutase, or catalase enzymes. Histopathological and immunohistochemical analyses indicated that cisplatin caused kidney damage, which was mostly prevented by resveratrol treatment. In conclusion, resveratrol ameliorates cisplatin-induced oxidative injury in the kidney of rabbit.

Attenuation of ischemia-reperfusion injury with Marrubium cordatum treatment in ovarian torsion-detorsion model in rabbits.

OBJECTIVE: To investigate protective effects of Marrubium cordatum extract on ovary torsion-detorsion. DESIGN: Controlled research study. SETTING: Marrubium cordatum extract was obtained by methanol extraction. ANIMAL(S): Six-month-old female New Zealand rabbits. INTERVENTION(S): In the first phase, antioxidant activity of M. cordatum extract was evaluated. In the second phase, M. cordatum extract at doses of 0, 250, 500, and 1,000 mg/kg was studied for dose determination. In the third phase, the protective role of M. cordatum on ovarian torsion-detorsion injury was evaluated in sham control, torsion-detorsion, torsion-detorsion +M. cordatum (1,000 mg/kg). MAIN OUTCOME MEASURE(S): 1,1-Diphenyl-2-picrylhydrazyl, nitric oxide radical scavenging activity, reducing power capacity, and total phenolic compounds were assayed. Glutathione, malondialdehyde, catalase, and glutathione peroxidase were measured. Histopathological examination was also conducted. RESULT(S): Marrubium cordatum significantly inhibited 1,1-diphenyl-2-picrylhydrazyl, nitric oxide radicals, and showed a powerful reducing activity. Marrubium cordatum did not adversely affect biochemical and histopathological parameters at all doses. Malondialdehyde level and catalase activity in the torsion-detorsion group were significantly increased compared with those of the sham group, whereas the glutathione level and glutathione peroxidase activity were significantly decreased compared with those of the sham group. Marrubium cordatum treatment significantly lowered the malondialdehyde level and catalase activity but increased the glutathione level in torsion-detorsion injury. Histopathologically, severe congestion, hemorrhage, edema, and leukocyte infiltration were observed in the torsion-detorsion group. Marrubium cordatum treatment ameliorated these alterations. CONCLUSION(S): Marrubium cordatum attenuates ischemia-reperfusion-induced biochemical and histopathological alterations.

Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit.

In this study, it was aimed to investigate the protective effect of caffeic acid phenethyl ester (CAPE) on cisplatin hepatotoxicity. Thirty New Zealand rabbits were divided into 5 groups as group 1 (saline-injected control, C), group 2 (1% ethanol; vehicle for CAPE, E), group 3 (CAPE), group 4 (cisplatin, CS) and group 5 (cisplatin plus CAPE, CS+CAPE). Cisplatin caused increased immunoreactivity against inducible nitric oxide synthase (iNOS), but CAPE treatment reduced the immunoreactive hepatocytes. Liver malondialdehide (MDA), nitric oxide (NO(.)) levels and xanthine oxidase (XO) activities were higher in CS than in groups C and E. Cisplatin treatment also significantly decreased the tissue reduced glutathione (GSH) concentration compared to groups C and E. CAPE administration normalized the tissue GSH level and XO activity in group CS+CAPE, whereas CAPE treatment did not affect MDA level in group CS+CAPE. In addition, CAPE treatment significantly depressed the cisplatin-induced NO(.) increase in group CS+CAPE. Histopathologically, cisplatin caused hydropic degenerations, necrosis in hepatocytes, sinusoidal congestion, Kupffer cell proliferation and mononuclear cell infiltration. These alterations were less severe in rabbits receiving CS+CAPE. Parallel to histopathology, cisplatin increased serum AST and ALT levels, whereas CAPE treatment significantly reduced cisplatin-induced AST and ALT rise in the serum. Results suggest that cisplatin causes oxidative and nitrosative damage to hepatocytes. Cisplatin-induced increase in XO and NO(.) could contribute oxidative stress in the hepatotoxicity. CAPE shows partial protection against cisplatin-associated biochemical and histopathological alterations.

Effects of organophosphate phenyl saligenin phosphate and polyether carboxylic ionophore lasalocid on motor nerve conduction velocity, neuropathy target esterase enzyme activity, and clinical ataxia in chickens.

Organophosphates (OP) are widely used chemicals in agriculture and industry. Some OPs produce a delayed type of neuropathy affecting human and animals following exposure. Subacute neurotoxic doses of some OPs can be potentiated by concomitant exposure to certain chemicals. Lasalocid is a polyether carboxylic ionophore used as a growth promotant and anti-coccidial in the cattle and poultry industries, respectively. Lasalocid is also known to induce peripheral neuropathy. Neurotoxicity of phenyl saligenin phosphate (PSP) and lasalocid and possible interaction were studied in chickens by evaluating motor nerve conduction velocity (MNCV), clinical ataxia, and neuropathy target esterase (NTE) enzyme activity. Forty-eight fryer chickens were divided into four groups as follows: Group 1 (control), group 2 was injected with single subcutaneous (s.c.) PSP (5 mg/kg), group 3 received oral lasalocid sodium (20 mg/kg, b.i.d., for 2 days), and group 4 received single s.c. PSP injection plus oral lasalocid sodium. MNCVs were decreased in groups 2, 3, and 4 compared to control. While there was no difference in MNCV between groups 2 and 3 (p > 0.05), MNCV in group 4 were significantly lower than in groups 2 and 3 (p < 0.05). NTE activities were significantly lower in PSP and PSP+lasalocid groups than in control and lasalocid group (p < 0.05). Onset of ataxia in group 4 appeared early and was exacerbated compared to groups 2 and 3. In conclusion, PSP and lasalocid could induce a significant decrease in MNCV and produce ataxia. Neuropathic OPs could be exacerbated by polyether ionophore lasalocid.

Effects of dietary zinc and L-arginine supplementation on total antioxidants capacity, lipid peroxidation, nitric oxide, egg weight, and blood biochemical values in Japanese quails.

The aim of this study was to evaluate effects of dietary zinc and L-arginine supplementation on blood total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), some blood chemistry parameters, and egg weights of laying quails. Three groups of Japanese quails were fed with a diet containing L-arginine (5 mg/kg), zinc (60 mg/kg), and normal basal diet (control) for 30 days. TAC, lipid peroxidation, and biochemical analysis were performed in the blood of animals. L-Arginine and zinc supplementation improved TAC and reduced MDA concentrations compared to the control (P<0.05). In comparison to the control, blood NO concentrations were increased by Larginine (P<0.01) and zinc treatment (P<0.05). Both zinc (P<0.001) and L-arginine (P< 0.01) supplementation significantly increased egg weight in laying quails. Some of the blood chemistry parameters were also altered by the treatment of L-arginine and zinc supplementation. No difference was found in blood albumin and creatinine levels among the groups. Blood glucose (P=0.833) and total protein (P=0.264) levels in control and Larginine-treated groups were found to be similar. Glucose and total protein levels were decreased in zinc-supplemented animals compared to the control and L-arginine groups (P< 0.05). No difference was found in triglyceride levels between control and zinc-applied groups (P=0.197). However, L-arginine treatment reduced the blood triglyceride levels compared to the control (P<0.05). In conclusion, L-arginine and zinc supplementation could be beneficial and effective for decreasing oxidative stress, boosting antioxidant capacity, and improving egg weight in the blood of the animals.

The effects of acute acetaminophen toxicity on hepatic mRNA expression of SOD, CAT, GSH-Px, and levels of peroxynitrite, nitric oxide, reduced glutathione, and malondialdehyde in rabbit.

We investigated the regulation of antioxidant system under acetaminophen (AAP) toxicity. Twelve male New Zealand rabbits were divided into two groups with the following treatments: Group 1 animals were intraperitoneally injected with single saline (control). Group 2 animals were treated with intraperitoneal injection of AAP at a dose of 250 mg/kg body weight. Four hours following the treatments, blood samples were collected and the rabbits were sacrificed to collect liver samples. Hepatocellular damage was evaluated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as histopathological examinations and immunohistochemical analysis. Tissue-reduced glutathione (GSH), nitric oxide (NO(.)), and malondialdehyde (MDA) levels were also measured. mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured by semi-quantitative RT-PCR. It was found that liver GSH was reduced significantly in AAP-treated rabbits (P < 0.05), while MDA and NO(.) levels were increased when they were compared to control (P < 0.05). Blood AST and ALT levels were also increased following AAP treatment (P < 0.05). Hepatocellular degeneration and severe necrosis were detected in histopathological examinations. Increased immunostaining was observed for inducible nitric oxide synthase (iNOS) and nitrotyrosine in the liver. There were no changes in mRNA expression levels of SOD, CAT, and GSH-Px after AAP treatment compared to control group. These results suggest that the expression of these enzymes, which are involved in the antioxidant system, may not be altered after AAP toxicity, although classical toxic changes such as depletion of GSH, hepatocellular necrosis, and increased immunostaining for iNOS and nitrotyrosine were detected.

Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice.

L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing the beta-oxidation of fatty acid in the mitochondria. It is also a known antioxidant with protective effects against lipid peroxidation. In this study, hepatoprotective effect of L-carnitine was investigated against acetaminophen (AA)-induced liver toxicity where mitochondrial dysfunction and oxidative stress are thought to be involved in AA hepatotoxicity. Sixty-four Balb/C mice were divided into eight groups. Mice were dosed with single-AA injection (500 mg/kg via the intra peritoneal route) with or without L-carnitine (500 mg/kg for 5 days starting 5 days before AA injection via intra peritoneal route) and sampled at 4, 8 and 24 h following AA injection. AA increased serum AST, ALT, total sialic acid (TSA) and MDA as well as tissue TSA and MDA levels significantly with the highest increase observed at 4 h, but there was a decrease in blood and tissue GSH level. Administration of L-carnitine significantly reduced AA-induced elevations in AST, ALT, TSA and MDA concentrations and increased GSH levels at all sampling points. AA also induced necrosis, hyperemia, sinusoidal congestion and hemorrhage with time-dependent increase in severity, but the degree of necrosis and histopathologic alterations were most severe at 24 h following AA administration. However, the degree of pathologic alterations was less severe with simultaneous L-carnitine application. These results suggest that AA results in oxidative damage in the liver with an acute effect. L-carnitine also has a prominent protective effect against AA toxicity and may be of therapeutic value in the treatment of AA-induced hepatotoxicity.

The effects of chronic exposure to ethanol and cigarette smoke on the formation of peroxynitrite, level of nitric oxide, xanthine oxidase and myeloperoxidase activities in rat kidney.

The aim of this study was to investigate the effects of chronic ethanol intake and cigarette smoke exposure on rat kidney. The animals were divided into four experimental groups: (1) the control group (C), (2) the ethanol group (E), (3) the cigarette smoke group (CS), and (4) the cigarette smoke plus ethanol group (CS+E). Rats in E, CS and CS+E groups were treated with ethanol and/or cigarette smoke for 6 months. The animals were killed and the kidneys were removed to determine the activity of xanthine oxidase (XO), myeloperoxidase (MPO) and the levels of nitric oxide (NO). Histopathological and immunohistochemical analysis were performed in kidney tissues. The activity of XO/g protein were 2.8 +/- 0.3, 5.2 +/- 0.3, 3.2 +/- 0.1, and 7.4 +/- 0.7 U for C, E, CS and CS+E groups, respectively. In groups E, and CS+E, the XO values were significantly higher than in group C (P < 0.05). The increase in XO activity of CS was not significantly different from group C (P > 0.05). There was a significant increase in XO activity of group CS+E as compared to CS and E groups (P < 0.05), and also a significant difference in XO activity between E and CS was observed (P < 0.05). The activity of MPO/g protein were 13.5 +/- 0.6, 16.2 +/- 1.1, 14.7 +/- 1.1, 23.8 +/- 0.9 U for C, E, CS, and CS+E groups, respectively. While MPO activity of kidneys from group CS+E were significantly higher as compared to C, CS, and E groups (P < 0.05), there was no significant difference among the groups of C, CS, E (P > 0.05). The levels of NO/g wet tissue were 347.7 +/- 8.5, 261.1 +/- 4.8, 329.8 +/- 5.6, and 254.2 +/- 3.8 nmol for C, E, CS, and CS+E groups, respectively. In groups of E and CS+E, the NO values were significantly lower than that of group C animals (P < 0.05). Although we detected lower NO levels in the E and CS+E groups than in CS group (P < 0.05), a significant difference in NO levels between CS+E and E groups was not observed. In the histopathological analysis of the kidney slices, severe degenerations in kidney tissues of group CS, E, CS+E were observed. Generally, the histological changes in kidney of CS+E and E groups were more severe than those observed in CS alone. While we observed a strong immunoreactivity for anti-nitrotyrosine antibody in kidneys of group CS+E, examination of sections from rat kidneys in group E revealed moderate staining. On the other hand, group CS had very little immunostaining. There was no immunostaining in group C. We concluded that chronic ethanol administration and cigarette smoke exposure may cause oxidative and nitrosative stress which lead to rat kidney damage.