Histochemical and histomorphological evidence of the modulating role of 1-isothiocyanate-4-methyl sulfonyl butane on cisplatin-induced testicular-pituitary axis degeneration and cholesterol homeostasis in male Sprague-Dawley rats.

BACKGROUND: This study examine the histochemical and histomorphological effect of 1-isothiocyanato-4-methyl sulfonyl butane (SFN) on cisplatin (CP) induced testicular alteration and cholesterol homeostasis. MATERIALS AND METHODS: Ninety adult-male Sprague-Dawley rats were randomized into nine groups of ten (n=10) rats each. Group A (control) received normal saline, group B received a single dose of 10mg/Kg body weight (bwt) CP (i.p.), group C received 50mg/Kg bwt of SFN, group D received 100mg/Kg bwt of SFN, group E received 10mg/Kg bwt CP and 50mg/Kg bwt of SFN, group F received 10mg/Kg bwt CP and 100mg/Kg bwt of SFN, group G received 10mg/Kg bwt CP and 50mg/Kg bwt vitamin C, group H received 50mg/Kg bwt of SFN and 10mg/Kg bwt CP, group I received 100mg/Kg bwt of SFN and 10mg/Kg bwt CP. The procedure lasted for 56 days. Testicular histomorphology and histochemistry, testicular testosterone, sperm parameters, total antioxidant status (TSA), total oxidant status (TOS), oxidative stress index (OSI), and serum lipid profile were examined. RESULTS: Cisplatin decrease intra-testicular testosterone, sperm quality, and expression of glycogen and increases testicular TOS and OSI, serum lipid profile, collagen, and disruption of germinal epithelium. However, the intervention of SFN reversed the effect of CP on testes' weight and volume, DSP, ESP, testosterone production, TAS, TOS, and OSI. Histoarchitectecture showing normal seminiferous tubules and even distribution of glycogen and collagen fibers. CONCLUSION: Treatment with SFN ameliorate CP-induced testicular toxicity by reversing the cytotoxic mechanisms of CP.

Vanillic acid and vitamin C attenuated di-2-ethylhexyl phthalate-induced testicular toxicity in adult male rats.

Abstract: Di-2-ethylhexyl phthalate (DEHP) is an extensively used plasticizer which has raised some concerns about its safety on human health. This study aimed at evaluating the effects of vanillic acid (VA) and vitamin C (VC) supplementation on DEHP-induced testicular toxicity. Thirty-five adult male Wistar rats were randomly divided into 7 groups (A-G) (n = 5) receiving distilled water; 250 mg/kg bw of DEHP only; 30 mg/kg bw of VA and 250 mg/kg bw of DEHP; 30 mg/kg bw of VC and 250 mg/kg bw of DEHP; 30 mg/kg bw of DEHP plus 30 mg/kg bw of VA and 30 mg/kg bw of VC; 30 mg/kg bw of VA only; and 30 mg/kg bw of VC only, respectively. At the end of the experiment, blood was taken from the heart via cardiac puncture and stored, semen was collected from the caudal epididymis for immediate sperm analysis, while the testes were excised and preserved for histological examination and biochemical analysis. The results showed a significant decrease (P < 0.05) in body weights, sperm motility, sperm volume, sperm viability and count, antioxidant levels, and reproductive hormonal levels, with a significant increase (P < 0.05) in sperm morphological defect and lipid peroxidation level in DEHP-only group compared with the control but was ameliorated after VA and VC administration compared to the DEHP-only treated animals. VA and VC supplementation attenuated the toxic effects of DEHP on the testicular functions, morphology, and semen characterization of the experimental adult male Wistar rats. Lay summary: Male infertility is considered when identifiable female causes of infertility are excluded and semen quantity and quality fail to fulfil World Health Organization criteria. From conception through to adulthood, people are exposed to limitless environmental toxicants among which di-2-ethylhexyl phthalate (DEHP) commonly found in personal care products, cosmetics, and medical devices is prevalent. The present study elaborated on the importance of taking antioxidant-rich foods containing vitamin C and vanillic acid, such as those found in various fruits, olives, whole wheat, and cereal grains, in combating infertility caused by environmental toxicants. An experiment was carried out on rats to see the effect of vanillic acid and vitamin C supplementation on preventing DEHP-induced testicular toxicity. The testicles and semen were analyzed from five rats in each treated and control groups. The data led us to conclude that vanillic acid and vitamin C supplementation do have attenuating effects on DEHP-induced testicular toxicity, due to their high antioxidant and anti-inflammatory properties.

Prenatal exposure of bonny light crude oil induces embryotoxicity, impaired cognitive functions and cortico-hippocampal neurodegeneration on fetal outcomes of pregnant sprague-dawley rats.

The low Sulfur level, heavy metals and easy production rate of Bonny Light Crude Oil (BLCO) makes it one of Nigeria's most explored oil. This study investigated the memory impairments, embryotoxicity and cortico-hippocampal neurodegeneration induced by prenatal exposure to BLCO of pregnant Sprague-Dawley (S-D) rats. Twenty pregnant rats were divided into 4 groups (A-D) of 5 rats each. Group A received normal saline as placebo. Group B-D received oral doses of BLCO at 0.73 ml/kg, 2 ml/kg and 3.8 ml/kg on pregnancy day 8-12.5 respectively. The pregnant rats were allowed to litter and nurse their pups. At 6 weeks postnatal life, twelve (12) selected young rats (n = 12) were accessed for behavioral study (Y-maze) and then sacrificed for biochemical and histological analysis. The results showed spontaneous abortion, still births and significantly reduced number of live births in the high dose group of BLCO compared to control. Length of gestation was significantly increased in the high dose group when compared to the control. CAT levels reduced significantly with concomitant increase in 8-OHdG among BLCO treated groups compared to control. Spontaneous alteration and number of arm entries decreased in the BLCO groups in comparison to control. Histological observation showed reduced cellular size, chromatolysis and presence of extracellular senile plaques in the prefrontal cortex and mild histological changes in the hippocampus architecture in the BLCO treated groups compared to the control. BLCO is capable of inducing embryotoxicity, impair cognition and cortico-hippocampal neurodegeneration.

Moringa oleifera restored semen quality, hormonal profile, and testicular morphology against Highly Active Antiretroviral Therapy-induced toxicity in adult male Wistar rats.

OBJECTIVE: Reproductive toxicity has been greatly linked with Highly Active Antiretroviral Therapy (HAART) use. This study investigated the effects of Moringa oleifera Leaf Extract (MOE) on HAART-induced testicular toxicity in adult male Wistar rats. METHODS: Twenty adult male Wistar rats (150-200 g) were assigned into four groups (n=5). Group A received distilled water; Group B received (orally) 200 mg/kg BW HAART only; Group C received (orally) 200 mg/kg BW HAART and 100 mg/kg BW MOE (low dose group) and Group D received (orally) 200 mg/kg BW HAART and 300 mg/kg BW MOE. At the end of the 28-day experiment, body and testicular weights were measured; serum and testis obtained were subjected to hormone profiling, biochemical and histological studies. RESULTS: HAART caused a significant decrease in body and testicular weight, testicular distortion and spermatogenic cell disorganization, altered semen quality and function, hormonal profiles, and oxidative stress markers (SOD, CAT, GSH) were significantly decreased with the concurrent increase in MDA level. However, treatment with MOE improved sperm parameters, testis morphology, antioxidants markers, and hormones assessments. CONCLUSIONS: The exposure to HAART produced marked testicular toxicity, ameliorated using Moringa oleifera leaf extract, thereby preserving testicular physiological function and morphology.

Exposure to pyrethroids induces behavioral impairments, neurofibrillary tangles and tau pathology in Alzheimer's type neurodegeneration in adult Wistar rats.

This study investigated the exposure of pyrethroids in the development of Alzheimer's type neurodegeneration by analyzing ß- amyloid, tau and Glial Fibrillary Acidic Protein (GFAP) in adult Wistar rats. Forty adult Wistar rats (130-150 g) of both sexes were assigned into five groups (n = 8). Groups A-C were treated with three different sub-lethal doses (75, 50 and 25%)of the pyrethroids formulation diluted with olive oil once/daily for 45 days, while groups D&E received olive oil and distilled water respectively (as control groups). During the treatments, physical clinical signs were monitored for cognitive behavioral studies involving object recognition tasks and novel object identification test. At the end of treatment, the rats were sacrificed by cervical dislocation, the brains were harvested and the hippocampus located and dissected out for immunohistochemical studies. Standard histochemical techniques were employed. The results showed a significant decrease (p ≤ 0.05) in the spontaneous alternation and discrimination index in the treatment groups when compared to the control groups. Histological observation showed nuclear fragmentation in treated rats in a dose dependent manner when compared to the controls. Amyloid plaques were further observed and markedly stained with Congo-red in the treated rats compared to the control groups. Immunohistochemical observation revealed that exposure to pyrethroids increased immunoreactivity of GFAP and tau protein in both CA3 and Dentate gyrus (DG) regions in the treated rats indicative of Alzheimer's type degenerative diseases.

Nutritional supplementation of gallic acid ameliorates Alzheimer-type hippocampal neurodegeneration and cognitive impairment induced by aluminum chloride exposure in adult Wistar rats.

Prolonged exposure to aluminum through occupational hazards or food/water intake has been linked to the occurrence of Alzheimer's disease (AD). This study aimed at investigating the neuroprotective effects of Gallic Acid (GA) against aluminum-chloride induced AD in adult Wistar rats. Twenty eight (28) adult Wistar rats were divided into four groups (n = 7). Group A received normal saline as placebo; Group B received 200 mg/kg bw of AlCl3 only; Group C received 100 mg/kg bw of GA only and group D received 100 mg/kg bw of GA and 200 mg/kg bw of AlCl3. At the end of the 60 days experiment, blood samples were collected to obtain serum for analysis and the brain was harvested. Neurobehavioural tests (Morris Water maze, Y-Maze), neurotransmitter levels, oxidative stress markers, serum electrolytes, antioxidant enzymes and histological assessment were carried out. There was a significant decrease in antioxidant enzymes (CAT, GSH and SOD), serum electrolyte (except K+) and neurotransmitter levels (except norepinephrine) with corresponding increase in stress markers (MDA, H2O2 and NO) among group B compared to control but was restored nearly to normal after GA administration. Neurobehavioral tests showed decreased spatial memory impairment and learning deficit in group B compared to control but was ameliorated with GA administration. Histological observation showed neurofibrillary tangles and amyloid plaques in the external granular layer of group B but protected by GA administration. Nutritional supplementation of GA preserve the morphological and physiological integrity of the hippocampus against environmental neurotoxins (AlCl3) by mopping up free radicals associated with oxidative stress induced AD.

Potentiating response of D- Ribose-L-Cysteine on Sodium arsenate- induced hormonal imbalance, spermatogenesis impairments and histomorphometric alterations in adult male Wistar rat.

OBJECTIVE: Reproductive toxicity is an important health challenge, mostly associated with exposure to several environmental toxicants. Arsenic is a ubiquitous toxic compound naturally present in the environment. This study was carried out to evaluate the dietary supplements of D-Ribose-L-Cysteine against sodium arsenate-induced testicular toxicity in adult male Wistar rats. METHODS: A total of 32 male rats (150-250g) were randomly divided into four (4) groups (n=8). Group A received normal saline as placebo; Group B received 8mg/kg BW of Sodium arsenate only; Group C received 8mg/kg BW of Sodium arsenate and 10 mg/kg BW of D-Ribose- L-cysteine; Group D received 8mg/kg BW of Sodium arsenate and 30 mg/kg BW of D-Ribose- L-cysteine. All administration was done via oral gavage for 28 days, thereafter the animals were sedated with pentobarbital sodium (intraperitoneally); we obtained testes and blood serum for analysis. RESULTS: The results showed abnormal testicular morphology with degeneration and decrease in spermatogonia, vacuolation and empty lumen, intense necrosis, spermatogenesis disruption (decrease sperm count, motility, viability) and degraded germinal epithelium of the seminiferous tubules, reduction in the hormone profile (FSH, LH, and TT) and oxidative stress parameters (CAT, GSH, and SOD) with a corresponding increase in MDA level in the arsenic-only treated rats (group B) compared to their control counterparts (group A), but it was ameliorated after DRLC administration, both in low and high doses, respectively. CONCLUSIONS: D-Ribose-L-Cysteine attenuated distorted testicular morphology, altered semen characteristics, hormone profile, and oxidative stress markers by preventing the deleterious toxicity of sodium arsenate.

Neurotherapeutic and antioxidant response of D-ribose-L-Cysteine nutritional dietary supplements on Alzheimer-type hippocampal neurodegeneration induced by cuprizone in adult male wistar rat model.

INTRODUCTION: Cuprizone is a neurotoxicant causing neurodegeneration through enzymes inhibition and oxidative stress. D-Ribose-L-Cysteine (DRLC) is a powerful antioxidant with neuroprotective properties. This study explored the antioxidant response of DRLC against cuprizone-induced behavioral alterations, biochemical imbalance and hippocampal neuronal damage in adult wistar rats. MATERIALS AND METHODS: Thirty two (32) adult male wistar rats (150-200g) were divided into four groups (n = 8). Group A received normal saline only as placebo; Group B received 0.5% cuprizone diet only; Group C received a combination of 0.5% cuprizone diet and 100 mg/kg bw of DRLC and Group D received 100 mg/kg bw of DRLC only. The administration was done through oral gavage once daily for 45 days. After the last treatment, neurobehavioral tests (Morris Water Maze and Y maze) was conducted; animals sacrificed and brain harvested for histological analysis and biochemical estimations of levels of antioxidants, oxidative stress markers, neurotransmitters and enzyme activitties. RESULTS: The results showed significant memory decline, hippocampal alterations, decrease levels of antioxidant markers, enzyme and neurotransmitters activities with concomitant increase in norepinephrine and oxidative stress markers in cuprizone induced rats relative to normal but was attenuated with DRLC administration. CONCLUSION: Cuprizone causes cognitive impairment and neurodegeneration through oxidative stress; however, administration of DRLC ameliorated neuropathological alteration induced by cuprizone.

Grape seed extract inhibits nucleus pulposus cell apoptosis and attenuates annular puncture induced intervertebral disc degeneration in rabbit model.

Low back pain is a musculoskeletal disorders implicated to disc degeneration. Grape seed extracts (GSEs) is a natural flavonoids rich compound with antioxidants and anti-inflammatory properties. This study is aimed at investigating the inhibitory and anabolic response of GSE on annular punctured induced disc degeneration in rabbit model. Twenty-Eight New Zealand white rabbits (weighing about 2.0-3.5 kg) were used with institutional animal care committee's approval. The animals were divided into four groups (n=7 per group). Group A (non-punctured group) received distilled water orally for 4 weeks. Group B (punctured group) received distilled water for 4 weeks. Group C (punctured treated group) received distilled water for 4 weeks and thereafter received 500 mg/kg of GSE for another 4 weeks. Group D received 500 mg/kg of GSE immediately after puncture for 4 weeks. At the end of the experiment, the animals were sacrificed with intramuscular injection of ketamine followed by intravenous injection of sodium pentobarbital. The percentage disc height index of the punctured group showed significant decrease compared to the control and treated groups. Histological and immunohistochemical studies showed distortion in the disc morphology, decrease in chondrocyte like cells, disorganization of collagen and elastic fibers, increase Bax expression levels in the punctured group compared to control and treated groups which was attenuated after GSE administration. GSE has preventive and restorative effects on punctured induced disc preventing the degradation of collagen fibrils within the disc tissues.

Grape seed extract inhibits nucleus pulposus cell apoptosis and attenuates annular puncture induced intervertebral disc degeneration in rabbit model / 대한해부학회지

Low back pain is a musculoskeletal disorders implicated to disc degeneration. Grape seed extracts (GSEs) is a natural flavonoids rich compound with antioxidants and anti-inflammatory properties. This study is aimed at investigating the inhibitory and anabolic response of GSE on annular punctured induced disc degeneration in rabbit model. TwentyEight New Zealand white rabbits (weighing about 2.0–3.5 kg) were used with institutional animal care committee’s approval. The animals were divided into four groups (n=7 per group). Group A (non-punctured group) received distilled water orally for 4 weeks. Group B (punctured group) received distilled water for 4 weeks. Group C (punctured treated group) received distilled water for 4 weeks and thereafter received 500 mg/kg of GSE for another 4 weeks. Group D received 500 mg/kg of GSE immediately after puncture for 4 weeks. At the end of the experiment, the animals were sacrificed with intramuscular injection of ketamine followed by intravenous injection of sodium pentobarbital. The percentage disc height index of the punctured group showed significant decrease compared to the control and treated groups. Histological and immunohistochemical studies showed distortion in the disc morphology, decrease in chondrocyte like cells, disorganization of collagen and elastic fibers, increase Bax expression levels in the punctured group compared to control and treated groups which was attenuated after GSE administration. GSE has preventive and restorative effects on punctured induced disc preventing the degradation of collagen fibrils within the disc tissues.

Grape seed extract inhibits nucleus pulposus cell apoptosis and attenuates annular puncture induced intervertebral disc degeneration in rabbit model / 대한해부학회지

Low back pain is a musculoskeletal disorders implicated to disc degeneration. Grape seed extracts (GSEs) is a natural flavonoids rich compound with antioxidants and anti-inflammatory properties. This study is aimed at investigating the inhibitory and anabolic response of GSE on annular punctured induced disc degeneration in rabbit model. TwentyEight New Zealand white rabbits (weighing about 2.0–3.5 kg) were used with institutional animal care committee’s approval. The animals were divided into four groups (n=7 per group). Group A (non-punctured group) received distilled water orally for 4 weeks. Group B (punctured group) received distilled water for 4 weeks. Group C (punctured treated group) received distilled water for 4 weeks and thereafter received 500 mg/kg of GSE for another 4 weeks. Group D received 500 mg/kg of GSE immediately after puncture for 4 weeks. At the end of the experiment, the animals were sacrificed with intramuscular injection of ketamine followed by intravenous injection of sodium pentobarbital. The percentage disc height index of the punctured group showed significant decrease compared to the control and treated groups. Histological and immunohistochemical studies showed distortion in the disc morphology, decrease in chondrocyte like cells, disorganization of collagen and elastic fibers, increase Bax expression levels in the punctured group compared to control and treated groups which was attenuated after GSE administration. GSE has preventive and restorative effects on punctured induced disc preventing the degradation of collagen fibrils within the disc tissues.

D-Ribose-L-Cysteine prevents intervertebral disc degeneration in annular puncture-induced rabbit model

Degeneration of the intervertebral discs is strongly implicated as the main cause of low back pain. To determine the preventive potential of D-Ribose-L-Cysteine in annular punctured intervertebral disc degeneration in rabbit model. Twenty New Zealand white rabbits (1.5 to 3.0 kg each) underwent annular puncture of the L2-L3, L3-L4, and L4-L5 discs. Group 1 (non-punctured control) were given phosphate-buffered saline; group 2 (model control) were given phosphate-buffered saline immediately after puncture for 4 weeks ; group 3 (punctured treated) were given 150 mg/kg/bw of D-Ribose-L-Cysteine solution immediately after puncture for 4 weeks; group 4 (punctured treated) were given 300 mg/kg/bw of D-Ribose-L-Cysteine solution immediately after puncture for 4 weeks. Rabbits were sacrificed at 4 weeks after puncture. The animals were housed individually in a meshed wire bottom cages with access to water and standard chow ad libitum. The serial X-rays were performed at 0 and 4 weeks for the rabbits and whole spinal column and discs were extracted and analyzed for various histological staining techniques (H&E and HVG), biochemical and immunohistochemical analysis. The X-rays showed a progressive decrease in disc height over timewhich was significantly prevented by the D-Ribose-L-Cysteine administration. The histological grade, collagen type 1 and 2, aggrecan, and matrix metalloprotease-13 mRNA expression and histological analysis were consistently indicative of degeneration, supporting the results of the X-ray data. This study has now documented that D-Ribose-L-Cysteine halts the progression of intervertebral disc degeneration and can be useful as prophylactic agents especially in people prone to disc degeneration

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Ageratum conyzoides attenuates alcohol induced liver toxicity in male Wistar rats.

BACKGROUND: Ageratum conyzoides (AC) is unique for its antioxidant activity and protective role to tissues. However this property is yet to be demonstrated in animals administered toxic alcohol concentrations. OBJECTIVE: To determine the effect of AC extract on the oxidative stress, liver enzymes and histology. METHODS: Twenty four male rats (190-230 g) were divided into three groups of eight rats. Group A (control) administered distilled water. Group B (ethanol group) received 10 g/kg body weight of ethanol. Group C (ethanol + AC group) were treated with ethanol (as above) and AC (250 mg/kg body weight) concurrently. Total experimental duration was 35 days at the end of which animals were euthanized by cervical dislocation. Liver and blood samples were taken and processed for: microscopic studies, estimation of activities of liver enzymes [alanine aminotransferase (AST), aspartate aminotransferase (ALT) and alkaline phosphatase (ALP)], Malondialdehyde (MDA) and antioxidants [Superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) and Catalase (CAT)] respectively. RESULTS: Compared to control, the rats treated with ethanol had significantly increased liver enzymes and MDA levels but these were decreased in ethanol + AC group compared to the ethanol group. The histologies of concurrent ethanol + AC treated group were similar to control groups. CONCLUSION: AC protects the liver against alcohol induced damage.