The protective effect of N-acetylcysteine against MK-801-induced neurodegeneration in mice.

BACKGROUND: Neurological disorders result in not only a decline in the quality of life of patients but also a global economic burden. Therefore, protective medicine becomes more important for society. MK-801 is a chemical agent used to understand the etiology of behavioral disorders and brain degeneration in animal models. This study aims to determine whether N-acetylcysteine (NAC) is useful to treat brain degeneration caused by MK-801, an N-methyl-D-aspartate glutamate receptor antagonist. METHODS AND RESULTS: Four groups were formed by dividing 24 male BALB/c mice into groups of six. The control group was given a saline solution (10 ml/kg-i.p.). MK-801 (1 mg/kg-i.p.) was given alone to one group, and it was given with NAC (100 mg/kg-i.p.) to another group, while the last group was given only NAC (100 mg/kg-i.p.). The administration of drugs lasted for fourteen days. After the behavioral tests (open field and elevated plus-maze), all animals were euthanised, and brain tissues were collected for real-time PCR, TAS-TOS analysis, hematoxylin-eosin, Kluver-Barrera, and TUNEL staining. In the MK-801 group, besides nuclear shrinkage in neurons, glial cell infiltration, vacuolization in cortical neurons, white matter damage, and apoptosis were observed. CONCLUSION: In the mice given NAC as a protective agent, it was observed that behavioral problems improved, antioxidant levels increased, and nuclear shrinkage, glial cell infiltration, vacuolization in neurons, and white matter degeneration were prevented. Moreover, MBP expression increased, and the number of TUNEL-positive cells significantly decreased. As a result, it was observed that NAC may have a protective effect against brain degeneration.

Protective role of the dried white mulberry extract on the reproductive damage and fertility in rats treated with carmustine.

The present study investigated the protective effect of dried white Mulberry extract (DWME) against carmustine (Crm) induced biochemical alterations and spermatological, histopathological, and fertility damage in Wistar albino rats. Male rats were divided into four groups (control, Crm, Crm + DWME, and DWME group). It was found that Crm decreased the motility. Crm decreased the concentration (not different from control group) compared to DWME groups. Total blood MDA levels were reduced during the recovery period. Also, the recovery period reduced the MDA levels in the Crm group/testicular tissue. The GSH levels in the Crm + DWME group were the highest among all groups in the testicular tissue/experiment period. In the immunohistochemical evaluation of the testicular tissue, a high level of caspase-3 was observed in the cells that underwent meiosis in the Crm group. The most pronounced DNA damage was also detected in the Crm group. The Crm + DWME group showed the highest number of offspring born during recovery period. In conclusion, dried white mulberry extract protects against the spermatological damages caused by carmustine. Moreover, recovery period played a positive effect on spermatological parameters and fertility.

The protective effects of erdosteine on subacute diazinon-induced oxidative stress and inflammation in rats.

In today's world, pesticides are commonly used to control pests and in advanced agriculture. As an organophosphorus insecticide (OPI), diazinon (DZN) is a commonly used substance. However, the widespread usage of DZN increases the probability of incidence of toxication. This toxication has been reported to be shaped not through cholinergic syndromes that are experienced as a result of acetylcholinesterase inhibition, which is the primary effect of these cases. It is rather shaped by the altering of the facilitation of oxidative stress and inflammatory response. In this study, the protective effect of administering erdosteine (ERDOS) subacute DZN exposure was investigated. A total of 24 male Wistar albino rats were separated into 4 groups (with 6 rats in each group), namely, the control, DZN (15 mg/kg/day), ERDOS (10 mg/kg/day), and DZN + ERDOS (15 mg/kg/day DZN + 10 mg/kg/day ERDOS) groups. These medications were given through oral gavage for 28 days. With the whole blood, plasma, and serum samples taken from the rats, oxidant-antioxidant parameters and cytokine levels were measured. The MDA and NOx levels and SOD and CAT enzyme activities of the DZN group were higher than those of the control group, while the GSH levels and TAC and GPx activities of the DZN group were lower than those of the control group (p < 0.05). It was also found that cytokine (IL-1ß, IL-10, and TNF-α) levels in the DZN group were higher than those in the control group (p < 0.05). On the other hand, the ERDOS implementations were detected to ameliorate the harmful effects of DZN on the oxidant-antioxidant parameters and cytokine levels (p < 0.05). Conclusively, besides the known mucolytic efficacy of ERDOS, it may also be stated to display free radical scavenger, antioxidant, and anti-inflammatory characteristics to inhibit some proinflammatory cytokines that are specifically involved in oxidative stress. Additionally, the ameliorating property of ERDOS can be benefited from in possible DZN-induced toxication cases.

Investigation of the protective effect of resveratrol in an MK-801-induced mouse model of schizophrenia.

Increasing evidence supports the view that oxidative stress and brain demyelination play an important role in the pathogenesis of schizophrenia. Resveratrol is a powerful antioxidant with neuroprotective effects. This study aimed to assess the effect of resveratrol on schizophrenia-like behaviors and possible brain demyelination induced by MK-801, an N-methyl-D-aspartate glutamate receptor antagonist, and the underlying neuroprotective mechanism. Resveratrol (40 mg/kg/day/, intraperitoneal) was administered to mice for 14 days. MK-801 (1 mg/kg/day, intraperitoneal) was injected into the mice 4 h after the resveratrol administration for 14 days. The open-field and elevated-plus maze tests were performed to detect behavior changes on the 15th day. Following the behavioral tests, the expression of the myelin basic protein (MBP) was measured with the real-time PCR (RT-PCR) method, while total oxidant capacity (TOS) and total antioxidant capacity (TAS), which are the biomarkers of oxidative damage, were measured with the ELISA method. Hematoxylin-eosin staining was also used to identify stereological and pathological changes in the brain. According to the results obtained, this study showed for the first time that resveratrol prevented glial cell infiltration induced in the brain by MK-801 and shrinkage of nerve cell nuclei in the hippocampus and corpus callosum. However, the resveratrol administrations did not correct behavioral disorders and demyelination of schizophrenia. Although resveratrol partially prevented oxidative damage in the brain in the mice that were injected with MK-801, it was determined that this effect was not statistically significant. These results showed that resveratrol administration partially protects tissues against MK-801-induced neurodegeneration, and resveratrol may be used in combination with different antioxidants or at different doses in future studies.

Red pine (Pinus brutia Ten) bark tree extract preserves sperm quality by reducing oxidative stress and preventing chromatin damage.

This study aimed to investigate the effectiveness of using red pine bark tree extract (P; Pinus brutia Ten) as a TRIS extender in an attempt to prevent oxidative stress in bull spermatozoa after freezing. Semen specimens were obtained from Simmental bulls via an artificial vagina and pooled. They were separated into five specimens and diluted with Tris extender consisting of P (200, 100, 50 and 25 µg/ml) and P free (control; C) up to a final concentration of 16 × 106 per straw. All specimens were equilibrated for a period of 4 hr at a temperature of 4°C, following which they were filled in 0.25-ml French straws and frozen. Addition of P resulted in favourable tail length in comparison with C (p < .05). The lowest malondialdehyde levels and the highest glutathione levels were detected in all P groups (p < .05). Supplementation with P did not show advanced results in terms of total, progressive sperm motility and total abnormality in comparison with C (p > .05). In conclusion, it has been shown that although P added to a Tris extender does not have a positive effect on sperm motility, it prevents chromatin damage by reducing oxidative stress, in addition to reducing head abnormalities when used at the amount of 50 µg/ml.

Determination of acute oral toxicity of glyphosate isopropylamine salt in rats.

In this study, we aim to determine the median lethal dose (LD50) of glyphosate isopropylamine salt (GI), which is commonly used in the world and especially in Turkey against to weeds, in male and female rats by using the probit or logit analysis method. A total of 140 Wistar rats were used, including 70 females and 70 males. To determine LD50, the male and female rats were randomized into 7 groups made up of 10 animals in each group. At doses of 6000, 6500, 7000, 7500, 8000, 8500, and 9000 mg / kg, GI was administered to the male and female rats by oral gavage. After dosing, the animals were periodically monitored for 14 days. No deaths were observed after 48 h of herbicide application. In this study, only logit analysis was used for the LD50 value to be calculated in the male rats within 24 h, while other analyses were carried out with the probit method. In the female and male rats, the LD50 levels of GI between 24 and 48 h were determined as 7444.26-7878.50 mg/kg and 7203.58-7397.25 mg/kg, respectively. According to these results, it was concluded that female rats are more sensitive to GI than male rats. We believe that the findings that were obtained will guide researchers, clinicians, and toxicologists through preventive and curative studies against acute poisoning that may occur with GI.

Protective effects of resveratrol on biomarkers of oxidative stress, biochemical and histopathological changes induced by sub-chronic oral glyphosate-based herbicide in rats.

The aim of this sub-chronic toxicity study is to determine the protective effects of Resveratrol (Res) on oxidative stress, biochemical and histopathological changes induced by glyphosate-based herbicide (GBH) in the blood, brain, heart, liver and renal tissues. A total of 28 male Wistar rats were equally divided into 4 groups so that each group included 7 rats. In the study, Group I (control group) was given normal rodent feed and tap water ad libitum. Group II (Res group) was given Res 20 mg kg-1, Group III (GBH group) was given GBH of 375 mg kg-1 to achieve 1/10 of Lethal Dose 50% (LD50), and Group IV (Res + GBH) was given Res 20 mg kg-1 and GBH 375 mg kg-1 with oral gavage once a day for 8 weeks. While GBH decreased the glutathione (GSH) levels in the blood, brain, heart, liver and renal tissues, it significantly increased malondialdehyde (MDA) levels. In contrast, the aforementioned parameters were seen to recover in the group to which Res was administered. Moreover, it was observed that Res improved the histopathological changes induced by GBH in rat tissues. In conclusion, Res prevents oxidative stress caused by GBH by preventing lipid peroxidation (LPO) and boosting the antioxidant defense system and decreases the damage in the brain, heart, liver and renal tissues of Wistar rats.

Antioxidant and cytoprotective effects of N-acetylcysteine against subchronic oral glyphosate-based herbicide-induced oxidative stress in rats.

It is claimed that oxidative stress has a prominent role in the mechanism of toxic effects formed by glyphosate-based herbicide (GBH) in living systems. A strong thiol compound, N-acetylcysteine (NAC), has antioxidative and cytoprotective properties. The objective in this subchronic toxicity study was to identify the prophylactic effect of NAC over histopathological changes and oxidative stress induced by GBH in blood, renal, liver, cardiac, and brain tissues. A sum of 28 male Wistar rats were divided into four equal groups, each containing 7 rats. During the study, group I (control group) was supplied with normal rodent bait and tap water ad libitum. The applied agents were 160 mg/kg NAC to group II, 375 mg/kg as equivalent to 1/10 of lethal dose 50% (LD50) of GBH to group III, and 160 mg/kg of NAC and 375 mg/kg of GBH together once per day as oral gavage to group IV for 8 weeks. While GBH decreased the levels of GSH in blood, liver, kidney, and brain tissues, it considerably increased malondialdehyde levels. On the contrary, these parameters happened to improve in the group supplied with NAC. Besides, it was seen that NAC was observed to improve the histopathologic changes in rat tissues induced by GBH. It was concluded that NAC protects oxidative stress and tissue damage induced by GBH in blood and tissue and this prophylactic effect could be attributed to its antioxidant and free radical sweeper character.

Effect of Boron on the Repair of Osteochondral Defect and Oxidative Stress in Rats: an Experimental Study.

The aim of this study was to investigate the effect of boron on the repair of osteochondral defect and also on some antioxidant and oxidant parameters of both cartilage tissue and blood. A total of 24 adult male Wistar rats weighing between 350 and 400 g were used in the study. Animals were randomly divided into control (n = 8), boron (n = 8) and hyaluronic acid (HA) groups (n = 8). Under general anesthesia, a cylindrical full-thickness osteochondral defect 1.5 mm in diameter and 2 mm in depth was formed using a drill on the anterior side of the articular surface of the femur condyle. Boron group received 0.1 ml (10 mg/kg) of boron and HA group received 0.1 ml of HA, whereas control group received 0.1 ml of physiological saline solution. All agents administered intraarticular route and once a week for four times. At the end of the third month, the animals were euthanized and blood and joint tissue malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase levels were measured. Defected femoral condyles of the rats were removed for a histopathological examination. Histopathology revealed that the total cartilage repair score of the HA group was better than those detected in boron and control groups. Blood and articular cartilage GSH, SOD, and catalase levels were higher in the boron and HA groups as compared to the control group, while MDA level was lower compared to the control group. In conclusion, it was suggested that boron was not as effective as HA in the repair of osteochondral defect, but its antioxidant property was superior to HA.

Protective effect of N-acetylcysteine on MK-801-induced testicular oxidative stress in mice.

Experimental studies indicate that MK-801 causes organ injury in schizophrenic mice testes although it is molecular mechanism has not been clearly defined. In this study, we investigated the probable protective effect of N-Acetylcysteine (NAC) against MK-801- induced testicular toxicity in mice. In total, 24 Balb/C male mice were divided into 4 equal groups: the animals in the control group (vehicle treated) were intraperitoneally given 10 mL/kg/day saline solution, the animals in the experiment groups were intraperitoneally given 1 mg/kg/day MK-801 alone, 100 mg/kg/day NAC alone and MK-801 by 1 mg/kg/day for 14 days. The level of the testes' total oxidant status (TOS) in mice that were treated with MK-801 was significantly higher than those level in the other groups while the total antioxidant status (TAS) levels decreased. In comparison to the MK-801 group, the TOS levels were lower, and the TAS levels increased in the MK-801 + NAC group. In the morphometric analysis, the diameter and epithelial height of the seminiferous tubules of the testes showed no significant changes after MK-801 administration. Conversely, the weights of the testes decreased significantly. In the treatment with NAC, the weights of testes significantly increased in comparison to the MK-801 group. The histopathological examination revealed necrobiotic and degenerative changes in the epithelial cells, vacuole formation within the seminiferous tubules, a decrease in the number of the spermatozoid, and disorganization in the basement membrane of the seminiferous tubules in the MK-801 group in comparison to the control group. Administration of NAC alleviated several negative effects of MK-801 on the testicular damage in mice. In conclusion, our results showed that NAC protected the mice against the testicular toxicity of MK-801 when it was administrated intraperitoneally.

The Effects of Boron on Arsenic-Induced Lipid Peroxidation and Antioxidant Status in Male and Female Rats.

The aim of the present study was to investigate the possible protective effects of boron, an antioxidant agent, against arsenic-induced oxidative stress in male and female rats. In total, 42 Wistar albino male and female rats were divided into three equal groups: The animals in the control group were given normal drinking water, the second group was given drinking water with 100 mg/L arsenic, and the third group was orally administered drinking water with 100 mg/kg boron together with arsenic. At the end of the 28-day experiment, arsenic increased lipid peroxidation and damage in the tissues of rats. However, boron treatment reversed this arsenic-induced lipid peroxidation and activities of antioxidant enzymes in rats. Moreover, boron exhibited a protective action against arsenic-induced histopathological changes in the tissues of rats. In conclusion, boron was found to be effective in protecting rats against arsenic-induced lipid peroxidation by enhancing antioxidant defense mechanisms.

Protective effect of polydatin, a natural precursor of resveratrol, against cisplatin-induced toxicity in rats.

The aim of the present study was to evaluate the possible protective effect of polydatin (PD) on cisplatin (Cis) induced oxidative stress in rats. Totally, thirty male Wistar albino rats were fed standard rodent diet and divided into 5 equal groups: the control group (vehicle treated) was treated with physiological saline for ten days both orally and intraperitoneally (i.p.), the second group was orally treated with physiological saline and 7 mg/kg single i.p. injection of Cis on the seventh day, and third, fourth, and fifth groups were treated orally PD at 25, 50, and 100 mg/kg/day, respectively for 10 days starting seven days before Cis injection and 7 mg/kg single i.p. Cis was injected on the seventh day. Cis resulted in significant increase malondialdehyde levels and decreased glutathione levels. In addition, Cis treatment decreased superoxide dismutase and catalase activities in erythrocyte and tissues. Also, Cis treatment caused to increase DNA damage and affected serum biochemical parameters whereas slightly decreased AchE activity. However, treatment of PD resulted in reversal of Cis-induced oxidative stress, lipid peroxidation, and activities of antioxidant enzymes. In conclusion, PD has protective effect in rats against Cis-induced oxidative stress, enhances antioxidant defence mechanism, and regenerates their tissues.

Dietary Yucca schidigera supplementation reduces arsenic-induced oxidative stress in Swiss albino mice.

The aim of this study was to clarify the effects of dietary supplementation with Yucca schidigera (Ys) on lipid peroxidation (LPO), antioxidant activity, some biochemical parameters and histopathological changes in arsenic-exposed mice. Forty Swiss albino male mice were divided into five equal groups. Group I (control group) was given normal diet and tap water for 28 days. Group II (arsenic group) was given normal diet and 100 mg/L arsenic along with drinking water for 28 days. Groups III-V were given three different doses of Ys (50, 100 and 200 mg/kg) in supplemented diet and arsenic (100 mg/L) along with drinking water throughout the entire period of 28 days. The arsenic significantly increased serum biochemical parameters and malondialdehyde levels in blood and tissue. However, arsenic significantly decreased tissue glutathione concentration, erythrocyte superoxide dismutase and catalase activities. In contrast, dietary supplementation of Ys, in a dose-dependent manner, resulted in reversal of arsenic-induced oxidative stress, LPO and activities of antioxidant enzymes. Moreover, Ys also exhibited protective action against the arsenic-induced focal gliosis and hyperemi in brain, necrosis and degeneration in liver, degeneration and dilatation in Bowman's capsule of kidney and hyaline degeneration in heart tissue of mice. Consequently, our results demonstrate that Ys especially high-dose supplementation in diet decreases arsenic-induced oxidative stress and enhances the antioxidant defence mechanism and regenerate of tissues in Swiss albino mice.