Water-soluble phenolics from Phoenix dactylifera fruits as potential reno-protective agent against cisplatin-induced toxicity: pre- and post-treatment strategies.

Nephrotoxicity is the major side effect of cisplatin, an effective platinum-based chemotherapeutic drug that is applicable in the treatment of several solid-tissue cancers. Studies have indicated that certain water-soluble phenolics offer renal protection. Thus, this study investigates the role of pre and post-treatment of rats with water-soluble phenolics from Phoenix dactylifera (PdP) against nephrotoxicity induced by cisplatin. Rats were either orally pretreated or post-treated with 200 mg/kg body weight of PdP before or after exposure to a single therapeutic dose of cisplatin (5 mg/kg body weight) for 7 successive days intraperitoneally. The protective effects of PdP against Cisplatin-induced nephrotoxicity was based on the evaluation of various biochemical and redox biomarkers, together with histopathological examination of kidney tissues. The composition, structural features, and antioxidative influence of PdP were determined based on chromatographic, spectroscopic, and in vitro antioxidative models. Cisplatin single exposure led to a substantial increase in the tested renal function biomarkers (uric acid, creatinine, and urea levels), associated with an increase in malondialdehyde indicating lipid peroxidation and a significant decline (p < 0.05) in reduced glutathione (GSH) levels in the renal tissue when compared with the control group. A marked decline exists in the kidney antioxidant enzymes (catalase, SOD, and GPx). Nevertheless, treatment with PdP significantly suppressed the heightened renal function markers, lipid peroxidation, and oxidative stress. Spectroscopic analysis revealed significant medicinal phenolics, and in vitro tests demonstrated antioxidative properties. Taken together, results from this study indicate that pre- and/or post-treatment strategies of PdP could serve therapeutic purposes in cisplatin-induced renal damage.

Xylopia aethiopica suppresses markers of oxidative stress, inflammation, and cell death in the brain of Wistar rats exposed to glyphosate.

The herbicide "Roundup" is used extensively in agriculture to control weeds. However, by translocation, it can be deposited in plants, their proceeds, and the soil, thus provoking organ toxicities in exposed individuals. Neurotoxicity among others is one of the side effects of roundup which has led to an increasing global concern about the contamination of food by herbicides. Xylopia aethiopica is known to have medicinal properties due to its antioxidative and anti-inflammatory properties, and it is hypothesized to neutralize roundup-induced neurotoxicity. Thirty-six (36) Wistar rats were used for this study. The animals were shared equally into six groups with six rats each. Glyphosate administration to three of the six groups was done orally and for 1 week. Either Xylopia aethiopica or vitamin C was co-administered to two of the three groups and also administered to two other groups and the final group served as the control. Our studies demonstrated that glyphosate administration led to a significant decrease in antioxidants such as catalase, superoxide dismutase, glutathione, and glutathione peroxidase. We also observed a significant increase in inflammatory markers such as tumor necrosis factor-α, interleukin 6, C-reactive protein, and immunohistochemical expression of caspase-3, cox-2, and p53 proteins (p < 0.05). However, Xylopia aethiopica co-administration with glyphosate was able to ameliorate the aforementioned changes when compared to the control (p < 0.05). Degenerative changes were also observed in the cerebellum, hippocampus, and cerebral cortex upon glyphosate administration. These changes were not observed in the groups treated with Xylopia aethiopica and vitamin C. Taken together, Xylopia aethiopica could possess anti-oxidative and anti-inflammatory properties that could be used in combating glyphosate neurotoxicity.

D-ribose-L-cysteine exhibits neuroprotective activity through inhibition of oxido-behavioral dysfunctions and modulated activities of neurotransmitters in the cerebellum of Juvenile mice exposed to ethanol.

Alcohol exposure to the cerebellum has been known to trigger cerebellar dysfunctions through several mechanisms. This present study was designed to evaluate the repealing effect of D-ribose-L-cysteine (DRLC) on alcohol-induced cerebellar dysfunctions in juvenile BALB/c mice. The animals were randomly divided into 4 groups (n = 10 per group). Mice were given oral administration of normal saline (control), DRLC (100 mg/kg, p.o), ethanol (0.2 mL of 10% w/v), or DRLC (100 mg/kg, p.o) + ethanol (0.2 mL of 10% w/v). On day 29 of the study (i.e., 24 h after the administration of the last respective doses), neurochemical quantification of the respective levels of serotonin and dopamine, lipid peroxidation, total antioxidant, superoxide dismutase, and glutathione peroxidase in the cerebellar tissues of the mice were analyzed. Compared with the saline-treated group, the studied neurochemical indices were modulated across the various experimental groups. The administration of ethanol significantly modulates the levels of monoamine neurotransmitters (serotonin and dopamine) as well as contents of total antioxidants, activities of superoxide dismutase, and glutathione peroxidase, with a concurrently increased level of lipid peroxidase in the cerebellar tissue of the mice. DRLC significantly reverses these effects in the DRLC + ethanol co-treated group. Combined exposure to DRLC + ethanol counteracts the deleterious effect of ethanol in the cerebellum of juvenile BALB/c mice via monoamine neurotransmitter, lipid peroxidation, total antioxidant status, superoxide dismutase, and glutathione peroxidase action pathways. Therefore, DRLC could be a pharmacologic or therapeutic agent in attenuating the deleterious effects of alcohol on the cerebellum.

Preliminary assessment of proanthocyanidin isolates of Vitis vinifera seed on the central nervous system of male Albino mice.

This study evaluated the potential neurobehavioral effects of proanthocyanidin-rich-fraction (PRF) obtained from Vitis vinifera seed in male Albino mice. Adult (2½- to 3-month old) male Albino mice were treated with PRF (200, 100, 50 mg/kg) and subjected to diverse behavioral models specially designed for the assessment of central nervous system-acting agents. One-shot intraperitoneal (i.p) injection of PRF (200 and 100 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing, and grooming), anxiety-like responses (% open-arm time, open-arm entries but decreased the total number of enclosed arm times). However, acute i.p administration of PRF decreased the total score of apomorphine-induced stereotyped behaviors, latency to hexobarbitone-induced sleep, and increased the total sleep duration. Moreover, indices of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) were decreased in the PRF treatment groups, especially the PRF (50 mg/kg)-treated mice. Based on these present findings, it could therefore be inferred that systemic administration of PRF of V. vinifera seed origin induces diverse modification on the behaviors of the treated mice stemming from anxiolytic, anticonvulsant, sedative, and decrease in core temperature.

Proanthocyanidin from Vitis vinifera attenuates memory impairment due to convulsive status epilepticus.

This study investigated the effects of proanthocyanidin-rich fraction (PRF) of Vitis vinifera seed extract on the markers of hippocampal-dependent memory in convulsive status epilepticus (CSE) rat model. One hundred juvenile Wistar rats were randomized into 6 groups. Group 1 (n = 10) received propylene glycol (PG 0.1 ml/100 g) intraperitoneally (i.p), while convulsion was induced in groups 2-6 (n = 18 each) using lithium (127 mg/kg i.p) and pilocarpine hydrochloride (40 mg/kg i.p). The established CSE rats in groups 2-6 received a daily treatment of PG (0.1 ml i.p), PRF (30 mg/kg i.p), PRF (20 mg/kg BW i.p), PRF (10 mg/kg BW i.p) or diazepam (5 mg/kg BW i.p) for seven days. Thereafter, they were kept untreated but with access to feed and water for 21 days. The control and CSE-treated rats were subjected to behavioral tests, while the biochemical and histomorphological evaluations of the hippocampus were done after the sacrifice. The results were presented as mean ±â€¯SEM in graphs or tables. The level of significance was considered when p < 0.05. There was significant decrease in the hippocampal-dependent memory, hippocampal weight and an increased malondialdehyde concentration following CSE. The activities of acetylcholinesterase decreased significantly in the PRF-treated CSE rats. The hippocampal glial cells and granule count increased significantly following CSE, with various neurodegenerative features in the CA1 of the hippocampus. These derangements were attenuated significantly following PRF treatment. Memory impairment following CSE may be attenuated with the administration of PRF from V. vinifera seed in rats.

Graded doses of grape seed methanol extract attenuated ataxic movement, cerebellocortical toxicity, and impairment following chronic carbamazepine treatment in male Wistar rats.

This study investigated the effects of chronic cotreatment of carbamazepine (CBZ) with grape seed methanolic extract (GSME) on the markers of neurotoxicity and motor coordination in male rats. Thirty male Wistar rats were randomized into 5 groups (n = 6) and treated orally with propylene glycol (PG 0.1 ml/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) for 28 days. Thereafter, the animals were subjected to motor-coordination tests and, eventually, sacrificed by cervical dislocation. The cranium was opened and the brain excised. The prefrontal cortex (PFC) and cerebellum were homogenized for the biochemical assessment, while representative brain was fixed in 10% neutral-buffered formalin for the histomorphological investigation. The results were presented as mean ±â€¯SEM, analyzed using one-way analysis of variance (ANOVA) and Student-Newman-Keuls post hoc analysis where appropriate, while p < 0.05 was considered statistically significant. Indices of motor coordination were significantly (p = 0.0014) impaired with a significant (p = 0.0001) increase in the concentration of malondialdehyde (MDA) in the PFC and cerebellar tissue. In addition, the activities of glutathione increased (p = 0.0001) significantly in the CBZ + GSME-treated rats. All these anomalies were attenuated in the CBZ + GSME treated rats. Coadministration of GSME with CBZ may ameliorate CBZ-induced neurotoxicity, histoarchitectural disorganization of PFC and cerebellum with resultant effect on fine motor actions.

Dexamethasone as endocrine disruptor; type I and type II (anti) oestrogenic actions on the ovary and uterus of adult Wistar rats (Rattus Novergicus).

OBJECTIVE: Dexamethasone is a widely used glucocorticoid, which has been prescribed increasingly in recent years. The effects of Dexamethasone on the ovary and uterus was investigated in present study. METHODS: Twenty (20) adult female Wistar rats, weighing 130-170 g were assigned to four (4) groups of five (5) animals each. The rats in the control group received saline, while the rats in the experimental group was subjected to oral treatment of dexamethasone of 12 mg/kg, 10 mg/kg, and 7 mg/kg doses daily for a period of 10 days, respectively. The rats were slaughtered after 24 hours of the last administration, and the uterus and ovaries were harvested following abdominal incision. Histological and biochemical investigations were carried out and the results were analyzed using ANOVA with the Graph-Pad prism software package 6. RESULTS: There was a significant decrease in the activities of the carbohydrate metabolic enzymes of the uterus in the dexamethasone-treated groups compared to the control group (p<0.05). Vacuolation, atrophy, thick epithelium, enlarged cells, inactive interstitial glands and follicular cyst, characterized the histological observation in the dexamethasone-treated groups in a dose-dependent manner. CONCLUSION: This present study revealed that high-dose dexamethasone causes multiple changes in the histological features of the ovary and uterus, exerting type I and type II anti-oestrogenic effects on the female reproductive compartment.

Morphine-alcohol treatment impairs cognitive functions and increases neuro-inflammatory responses in the medial prefrontal cortex of juvenile male rats / 대한해부학회지

In the developed and developing world, opioid consumption in combination with alcohol has become one of the substances abused. In this experiment, we examined the effects of alcohol, morphine, and morphine+alcohol combination on cognitive functions and neuroinflammatory responses in the medial prefrontal cortex (mPFC) of juvenile male rats. Alcohol (1.0 ml of 15% v/v ethanol twice daily, subcutaneously, 7 hours apart), morphine (0.5 ml/kg of 0.4 mg/kg morphine chlorate twice daily, subcutaneously, 7 hours apart), morphine+alcohol co-treatment (0.5 ml/kg of 0.4 mg/kg morphine chlorate+1.0 ml of 15% v/v ethanol twice daily, subcutaneously, 7 hours apart) were administered for 21 days. Treatment with morphine+alcohol significantly impairs cognition functions in the Morris water maze, passive avoidance, and novel object recognition tests, furthermore, the treatment significantly increased the quantitative count of astrocytic cells and also conferred marked neuronal cell death in the mPFC, which were studied by glial fibrillary acidic protein immunochemistry for astrocytes and Cresyl violet for Nissl's substance distribution in neurons respectively. These results suggest that alcohol, morphine, and morphine+alcohol co-treatment may trigger cognitive deficits and neuroinflammatory responses in the brain.