Oxidative response to accumulation of trace metals in tissue of two bivalves, the Asian green mussel Perna viridis and the blood cockle Tegillarca granosa, living in Pattani Bay, Thailand.

OBJECTIVE: Using bivalves to indicate aquatic pollutants was favorable for discerning the negative effects of high levels of metal accumulation in tissue. We investigated the correlation between trace metal accumulation and the tissue oxidative response of two bivalves. METHODS: The Asian green mussel Perna viridis and the blood cockle Tegillarca granosa were sampled along with seawater and sediments from three locations around Pattani Bay, Thailand. Accumulation of nine trace metals (cadmium, cobalt, copper, chromium, nickel, manganese, iron, zinc, and lead) in seawater, sediments, and tissue and the oxidative tissue response were evaluated. Metal bioaccumulation factor, biota-sediment accumulation factor, and histopathology were also indicated. RESULT: The present study found that P. viridis and T. granosa were macroconcentrators and bioaccumulative of cadmium, and their tissue accumulation of cadmium was strongly related to lipid peroxidation activation. Perna viridis exhibited a higher oxidative response than T. granosa, as indicated by malondialdehyde, catalase, and reduced glutathione levels. CONCLUSION: The present study indicated that P. viridis and T. granosa were macroconcentrators and bioaccumulative of cadmium, and their tissue accumulation of cadmium was strongly related to lipid peroxidation activation. Research has shown discernible negative effects of a high level of metal accumulation in tissue, and deformed and damaged tissues were present in the gills, digestive glands, intestines, and feet of P. viridis and T. granosa.

Benefits of p-coumaric acid in mice with rotenone-induced neurodegeneration.

The paper examines the use of natural antioxidant and anti-inflammation substances as therapeutic candidates for brain disease. Para-coumaric acid (pCA), a phenolic compound with a variety of medicinal properties, was used against deterioration caused by various diseases. Recently, pCA has gained attention for use against cardiovascular disease but less so for neurodegenerative disease (i.e., Parkinson's disease). Therefore, the present study intended to investigate the effect of pCA against rotenone-induced Parkinson's disease-like pathology in mice. Thirty male institute of cancer research (ICR) mice were randomly divided into three experimental groups: Sham-veh, Rot-veh, and Rot-pCA100. Rotenone (Rot) 2.5 mg/kg was subcutaneously injected every 48 h in the rotenone groups. Alternately, a 100 mg/kg pCA dose was given every 48 h via intragastric gavage to the Rot-pCA100 group for 6 weeks. Motor ability was assessed at the second, fourth, and sixth week before brain collection for biochemical and histological analyses. Results indicated significant motor deficits appeared from the second to sixth week after rotenone injection. Brain analysis detected a significant effect of rotenone in the increase of malondialdehyde and tumor necrosis factor-alpha (TNF-α). This result was observed in accordance with a reduction of tyrosine hydroxylase (TH) and an increase of neuronal degeneration in the substantia nigra par compacta (SNc) and striatum. However, pCA was able to reverse all of the deterioration (i.e., reduced malondialdehyde and TNF-α) rotenone had caused, and it protected against TH and neuronal loss in the SNc and striatum. Therefore, the present study has depicted the neuroprotective effect of pCA against rotenone-induced Parkinson's disease-like pathology in mice. Benefits of pCA include anti-lipid peroxidation and anti-inflammatory effects, inhibition of neurodegeneration, and a nurturing effect on the TH level in the SNc and striatum, leading to mitigation of motor deficits.

Nanostructure lipid carriers enhance alpha-mangostin neuroprotective efficacy in mice with rotenone-induced neurodegeneration.

Neurodegenerative disease, for instance, Parkinson's disease (PD), is associated with substantia nigra dopaminergic neuronal loss with subsequent striatal dopamine reduction, leading to motor deficits. Currently, there is no available effective therapy for PD; thus, novel therapeutic agents such as natural antioxidants with neuroprotective effects are emerging. Alpha-mangostin (αM) is a xanthone derivative compound from mangosteen peel with a cytoprotective effect depicted in neurodegenerative disease models. However, αM has low aqueous solubility and low biodistribution in the brain. Nanostructured lipid carriers (NLC) have been used to encapsulate bioactive compounds delivered to target organs to improve the oral bioavailability and effectiveness. This study aimed to investigate the effect of αM and αM encapsulated in NLC (αM-NLC) in mice with rotenone-induced PD-like neurodegeneration. Forty male ICR mice were divided into normal, PD, PD + αM, and PD + αM-NLC groups. Vehicle, αM (25 mg/kg/48 h), and αM-NLC (25 mg/kg/48 h) were orally administered, along with PD induction by intraperitoneal injection of rotenone (2.5 mg/kg/48 h) for 4 consecutive weeks. Motor abilities were assessed once a week using rotarod and hanging wire tests. Biochemical analysis of brain oxidative status was conducted, and neuronal populations in substantia nigra par compacta (SNc), striatum, and motor cortex were evaluated using Nissl staining. Tyrosine hydroxylase (TH) immunostaining of SNc and striatum was also evaluated. Results showed that rotenone significantly induced motor deficits concurrent with significant SNc, striatum, and motor cortex neuronal reduction and significantly decreased TH intensity in SNc (p < 0.05). The significant reduction of brain superoxide dismutase activity (p < 0.05) was also detected. Administrations of αM and αM-NLC significantly reduced motor deficits, prevented the reduction of TH intensity in SNc and striatum, and prevented the reduction of neurons in SNc (p < 0.05). Only αM-NLC significantly prevented the reduction of neurons in both striatum and motor cortex (p < 0.05). These were found concurrent with significantly reduced malondialdehyde level and increased catalase and superoxide dismutase activities (p < 0.05). Therefore, this study depicted the neuroprotective effect of αM and αM-NLC against rotenone-induced PD-like neurodegeneration in mice. We indicated an involvement of NLC, emphasizing the protective effect of αM against oxidative stress. Moreover, αM-NLC exhibited broad protection against rotenone-induced neurodegeneration that was not limited to nigrostriatal structures and emphasized the benefit of NLC in enhancing αM neuroprotective effects.

Benefits of betanin in rotenone-induced Parkinson mice.

The present study aimed to investigate betanin's neuroprotective effect in mice with rotenone-induced Parkinson-like motor dysfunction and neurodegeneration. Forty male ICR mice were divided into 4 groups: Sham-veh, Rot-veh, Rot-Bet100 and Rot-Bet200. Rotenone at 2.5 mg/kg/48 h was subcutaneous injected in Rot groups, and betanin at 100 and 200 mg/kg/48 h were given alternately with the rotenone injections in Bet groups for 6 weeks. Motor dysfunctions were evaluated weekly using hanging wire and rotarod tests. Brain oxidative status including malondialdehyde, reduced glutathione, catalase, superoxide dismutase, with neuronal degeneration in the motor cortex, striatum and substantia nigra par compacta were evaluated. The immunohistochemical densities of tyrosine hydroxylase in striatum and in substantia nigra par compacta were also measured. We found that rotenone significantly decreased the time to fall in a hanging wire test after the 4th week and after the rotarod test at the 6th week (p < 0.05). The percentage of neuronal degeneration in substantia nigra par compacta, striatum and motor cortex significantly increased (p < 0.05), and the tyrosine hydroxylase density in substantia nigra par compacta and in striatum significantly decreased (p < 0.05). Betanin at 100 and 200 mg/kg significantly prevented substantia nigra par compacta, striatum and motor cortex neuronal degeneration (p < 0.05) and maintained tyrosine hydroxylase density in substantia nigra par compacta and in striatum (p < 0.05). These findings appeared concurrently with improved effects on the time to fall in hanging wire and rotarod tests (p < 0.05). Treatment with betanin significantly prevented increased malondialdehyde levels and boosted reduced glutathione, catalase and superoxide dismutase activities (p < 0.05). Betanin exhibits neuroprotective effects against rotenone-induced Parkinson in mice regarding both motor dysfunction and neurodegeneration. Betanin's neurohealth benefit relates to its powerful antioxidative property. Therefore, betanin use in neurodegenerative disease is interesting to study.

The neuroprotective effect of betanin in trimethyltin-induced neurodegeneration in mice.

Betanin, a natural food colorant with powerful antioxidative properties, has not been studied in terms of neurodegenerative disease intervention. Therefore, the present study aimed to investigate the neuroprotective effects of betanin against trimethyltin chloride (TMT) -induced neurodegeneration in mice. Forty male ICR mice were randomly divided into four groups: Sham-veh, TMT-veh, TMT-Bet50 and TMT-Bet100. In the TMT groups, neurodegeneration was induced with a one-time intraperitoneal injection of 2.6 mg/kg TMT. Betanin-treated groups (Bet) were given oral doses of 50 or 100 mg/kg dissolved in normal saline solution. Administrations were started 24 h prior to TMT injection and continued for 2 weeks. Anxious behavior and spatial cognition were evaluated, respectively. After behavioral tests, brain oxidative status, hippocampal histology and choline acetyltransferase (ChAT) activity were evaluated. Results showed that TMT significant induce anxious behavior and spatial learning and memory deficits (p < 0.05). These were found concurrently with significant decreases in CA1 ChAT activity, brain tissue catalase (CAT) and superoxide dismutase (SOD) activities with significant increase in hippocampal CA1 degeneration (p < 0.05). Betanin 100 mg/kg exhibited significant anxiolytic effect, preventive effect on CA1 degeneration and CA1 ChAT activity alteration as well as improvement of spatial learning and memory deficits (p < 0.05). These were found concurrently with significant increases of reduced glutathione, CAT and SOD activities as well as the decrease in malondialdehyde (p < 0.05). We conclude that betanin 100 mg/kg exhibits neuroprotective effects against TMT-induced neurodegeneration in mice via its anti-oxidative properties, protective against hippocampal CA1 degeneration and ChAT activity alteration. Therefore, betanin is interesting in further neurodegenerative therapeutic study and applications.

Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia reperfusion injuries.

Cerebral ischemia reperfusion (IR) is associated with neuronal death, which leads to disability and cognitive decline. The pathomechanism occurs because ischemia is exacerbated during the reperfusion period. Neuronal damage susceptibility depends on the affected brain areas and the duration of ischemia. Prevention and supplementation to neurons may help them endure during IR and further benefit them in rehabilitation. We investigated the protective effect of p-coumaric acid (PC) on cerebral IR injuries in mice. We randomly divided 30 male ICR mice into 3 groups of Sham (received vehicle and not induced IR), Control-IR (received vehicle and induced IR) and PC-IR (received 100 mg/kg PC and induced IR). We orally administered vehicle or 100 mg/kg of p-coumaric acid for 2 weeks before inducing the cerebral IR injuries by using 30 min of a bilateral common carotid artery occlusion followed by a 45-min reperfusion. We induced the IR condition in the Control-IR and PC-IR groups but not the Sham group, and only the PC-IR group received p-coumaric acid. After IR induction, we sacrificed all the mice and collected their brain tissues to evaluate their oxidative statuses, whole brain infarctions and vulnerable neuronal deaths. We studied the whole-brain infarction volume by 2, 3, 5-triethyltetrazoliumchloride staining of sections. We performed a histological investigation of the vulnerable neuronal population in the dorsal hippocampus by staining brain sections with 0.1% cresyl violet. The results indicated that IR caused significant increases in calcium and malondialdehyde (MDA) levels, whole brain infarction volume and hippocampal neuronal death. Pretreatment with p-coumaric acid significantly reduced MDA levels, whole-brain infarction volume and hippocampal neuronal death together and increased catalase and superoxide dismutase activities. We conclude here that pretreating animals with p-coumaric acid can prevent IR-induced brain oxidative stress, infarction size and neuronal vulnerability to death in cerebral IR injuries.

Beta-sitosterol mitigates cognitive deficit and hippocampal neurodegeneration in mice with trimethyltin-induced toxicity.

The present study investigated the neural health benefit of beta-sitosterol (BSS) against trimethyltin (TMT)-induced neurodegeneration in mice. Forty male ICR mice were randomly divided into Sham-veh, TMT-veh, TMT-BSS50, and TMT-BSS100. A one-time intraperitoneal injection of 2.6 mg/kg of TMT was given to mice in TMT groups. Vehicle (veh), BSS 50 mg/kg or BSS 100 mg/kg were orally given for 2 weeks. Spatial learning and memory were evaluated. Brain oxidative status, hippocampal neuropathology, and reactive astrocytes were done. White matter pathology was also evaluated. The results indicated the massy effect of TMT on induced motor ability and spatial memory deficits in accordance with increased neuronal degeneration in CA1, CA3, and DG and internal capsule white matter damage. TMT also induced the reduction of reactive astrocytes in CA1 and DG. Brain's catalase activity was significantly reduced by TMT, but not in mice with BSS treatments. Both doses of BSS treatment exhibited improvement in motor ability and spatial memory deficits in accordance with the activation of reactive astrocytes in CA1, CA3, and DG. However, they successfully prevented the increase of neuronal degeneration in CA1 found only with the BSS dose of 100 mg/kg, and it was indicated as the effective dose for neuroprotection in the vulnerable brain area. This study demonstrated mitigative effects of BSS against motor ability and memory deficits with neural health benefits, including a protective effect against CA1 neurodegeneration and a nurturing effect on hippocampal reactive astrocytes.

Neuroprotective effect of gallic acid in mice with rotenone-induced neurodegeneration.

We investigated the effect of gallic acid against neurodegenerative pathophysiology relevant to PD in mice with rotenone-induced toxicity. Forty male ICR mice were randomly divided into four groups: sham-veh, PD-veh (received subcutaneous injection with 2.5 mg/kg/48 h of rotenone); PD-Gal50; and PD-Gal100 (the latter two groups received subcutaneous injection with 2.5 mg/kg/48 h of rotenone and oral gavage with gallic acid 50 and 100 mg/kg/48 h, respectively). All treatments continued for 5 weeks with motor ability assessments once per week using hanging and rotarod tests. Brain tissue evaluation of oxidative status, together with striatal and substantia nigra par compacta (SNc) histological and immunohistological assessments were performed. The results indicate that rotenone significantly induced muscle weakness and motor coordination deficit from the first week of rotenone injection, and a significant increase in neuronal degeneration was presented in both the striatum and SNc. Decreased tyrosine hydroxylase and increment of glia fibrillary acidic protein expression in SNc were depicted. The deteriorating effects of rotenone were ameliorated by gallic acid treatment, especially 100 mg/kg dose. Rotenone did not induce a significant change of lipid peroxidation indicated, but gallic acid exhibited a significant inhibitory effect on the lipid peroxidation increment. Rotenone showed a significant reduction of superoxide dismutase activity, and neither 50 nor 100 mg/kg of gallic acid could alleviate this enzyme activity. In conclusion, gallic acid ameliorated motor deficits and preserving SNc neurons which led to maintaining of the dopaminergic source, including a nurturing effect on supporting astrocytes in mice with rotenone-induced neurodegeneration.

Neuroprotective effects of betanin in mice with cerebral ischemia-reperfusion injury.

Cerebral ischemia reperfusion (IR) injury as found in stroke is a complex and heterogeneous disorder and closely related to disability and death. Today, nutraceuticals and protective therapy to increase neuronal integrity and prevent pathological complication are common. We investigated the neuroprotective effect of betanin against cerebral IR injury in mice. Forty male institute of cancer research (ICR) mice were divided into Sham-veh, IR-veh, IR-Bet50 and IR-Bet100 groups. After 2 weeks of oral administration of normal saline (vehicle; veh) or 50 mg/kg or 100 mg/kg of betanin (Bet), mice were subjected to IR induction using 30-min bilateral common carotid artery occlusion, followed by 24 h of reperfusion. Brain infarction, oxidative status, cortical and hippocampal neurons and white matter pathologies were evaluated. Results showed that IR significantly increases brain infarction, Cornus Ammonis 1 (CA1) hippocampal and corpus callosum (CC) and internal capsule (IC) white matter degeneration (P<0.05). Brain oxidative status revealed significant elevation of malondialdehyde (MDA) together with a significant decrease in catalase (CAT) activity, induced by IR (P<0.05). Pretreatment with betanin 100 mg/kg led to a significant reduction in brain infarction and MDA, CA1 hippocampus, CC and IC white matter degeneration. Betanin also led to a significant increase in CAT activity (P<0.05), with enhancing effect on reduced glutathione levels (GSH, P<0.05). The present study revealed the neuroprotective efficacy of betanin against IR injury in mice's brains, including its inhibition of lipid peroxidation, and boosting of GSH and CAT activity.

Benefits of Erinacines from Different Cultivate Formulas on Cognitive Deficits and Anxiety-Like Behaviour in Mice with Trimethyltin-Induced Toxicity.

We investigated the neurological effects of the varied erinacine composition of different mycelia cultures in mice with trimethyltin (TMT)-induced neurodegeneration. Forty male ICR mice were randomly divided into five groups of Sham-veh, TMT-veh, TMT-EME, TMT-EMR and TMT-EME/R. The TMT groups received 2.6 mg/kg one-time intraperitoneal injections of TMT. Oral dosages of 200 mg/kg erinacine combination from each Hericium erinaceus mycelia (EM) cultivated formula (100% eucalyptus wood [E], 100% rubber wood [R], or 40% eucalyptus wood/60% rubber wood [E/R]) were given for two weeks. Spatial learning, memory, flexibility, and anxious behaviour were evaluated alongside brain tissues' oxidative status and histological analyses. Erinacine composition from EME/R exhibited significant positive effects on spatial learning, memory, flexibility, and anxiety (p < 0.05). These findings emerged concurrently with the significant mitigation of hippocampal lipid peroxidation, CA1 hippocampal, cortical neuron, and corpus callosum white matter degeneration (p < 0.05). These neurological benefits were associated with the EME/R composition of erinacine A, C, D, G, H, I, K and R. The best neuroprotective effect against TMT-induced neurodegeneration in mice is offered by the EME/R erinacine composition according to its anti-lipid peroxidation, its nurturing effect on neuronal and white matter, and mitigation of behavioural deficits.

Neuroprotective effects of Tiliacora triandra leaf extract in a mice model of cerebral ischemia reperfusion.

OBJECTIVE: The present study investigated possible neuroprotective effects of ethanolic extract of Tiliacora triandra leaf against cerebral ischemic-reperfusion injury in mice. MATERIALS AND METHODS: Forty male Institute of Cancer Research (ICR) mice were randomly divided into five groups: (1) Sham + 10% Tween 80, (2) bilateral common carotid artery occlusion (BCCAO) + 10% Tween 80, (3) BCCAO + T. triandra 300 mg/kg, (4) BCCAO + T. triandra 600 mg/kg and (5) BCCAO + quercetin 10 mg/kg. Cerebral ischemic-reperfusion (IR) was induced by 30 min of BCCAO followed by 45 min of reperfusion. After IR induction, total brain protein, calcium, malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH), as well as brain infraction and histopathological changes in vulnerable brain areas, such as the cerebral cortex and hippocampus, were evaluated. RESULTS: The results showed that 2 weeks of pretreatment with T. triandra leaf extract at doses of 300 and 600 mg/kg significantly reduced calcium and MDA, but increased GSH and SOD and CAT activities. The extract significantly attenuated brain infarction and neuronal death in the cerebral cortex and hippocampus. CONCLUSION: We demonstrated the neuroprotective effects of T. triandra leaf extract against cerebral IR injury in mice.

Neurological Changes in Vulnerable Brain Areas of Chronic Cerebral Hypoperfusion Mice.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is associated with neurological changes and cognitive decline. It is a major cause of vascular dementia and a contributing factor in Alzheimer disease. Animal models are useful in helping to elucidate the mechanisms of these diseases while demonstrating differences in pathological onset and severity. Furthermore, different mouse strains show differences in their susceptibility to neurological damage resulting in different cognitive outcomes. PURPOSE: This study investigated the effect of CCH induced by permanent unilateral common carotid artery occlusion (UCO) on neurological damage in vulnerable brain regions such as hippocampus, striatum, and white matter areas from 2 to 8 weeks following CCH induction. METHODS: Thirty-six male Institute of Cancer Research (ICR) mice were randomly divided into 2 main experimental groups, Sham and UCO. These 2 main groups were further divided into 3 observation periods of 2, 4, and 8 weeks following CCH. Histological study was then employed using 0.1% cresyl violet and luxol fast blue staining to assess neurological damage. RESULTS: We found equal levels of neurological damage induced by CCH between ipsi- and contralateral hemispheres. Hippocampus and striatum damage were slightly increased from 2 to 8 weeks rising to significance at 8 weeks in both areas, while the white matter densities of the corpus callosum, internal capsule, optic tract and striatum fiber did not change. CONCLUSION: CCH induced by UCO in ICR mice induces hippocampal and striatal damage at 8 weeks while leaving white matter undamaged.

Effect of Centella asiatica on pathophysiology of mild chronic cerebral hypoperfusion in rats.

OBJECTIVE: The present study investigated the effect of standardized Centella asiatica extract on cognition and hippocampal pathology of mild chronic cerebral hypoperfusion (CCH) that was induced by permanent right common carotid artery occlusion (RCO) in rats. MATERIALS AND METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into four groups of Sham-veh, Sham-C. asiatica, RCO-veh and RCO-C. asiatica, which were further divided into short-term and long-term CCH induction. Oral treatments with 20 mg/kg C. asiatica initiated 24 hours and 12 months after CCH and continued for 14 consecutive days. According to the cognition and histopathological evaluation period, the experiment was divided into 2 sets of either 2 or 12 months of CCH. RESULTS: Results showed that 2-month CCH induced learning flexibility deficit associated with CA1 neuronal damage and internal capsule (IC) astroglia activation. Long-lasting (12 months) mild CCH induced spatial learning, memory and flexibility deficits associated with progressive dorsal hippocampal damage. Treatment with 20 mg/kg of C. asiatica improved learning flexibility deficit after 2 and 12 months of CCH. C. asiatica ameliorated neuronal damage in the dorsal hippocampus at 2 months of CCH when given 24 hours after CCH onset. Treatment with C. asiatica after 12 months of cerebral blood flow reduction improved memory and learning flexibility deficits and was associated with the dentate gyrus neuronal damage reduction. CONCLUSION: Our finding indicates the therapeutic potential of C. asiatica either when given immediately after ischemic insult or when administered one year after ischemic insult, in a CCH rat model.

Tiliacora triandra (Colebr.) Diels leaf extract enhances spatial learning and learning flexibility, and prevents dentate gyrus neuronal damage induced by cerebral ischemia/reperfusion injury in mice.

OBJECTIVE: The present study investigated the effects of a local Thai vegetable, Tiliacora triandra (Colebr.) Diels, also known as Yanang, against cerebral ischemia/reperfusion injury in mice. MATERIALS AND METHODS: Thirty male ICR mice were divided into three experimental groups of BLCCAO + 10% Tween 80, BLCCAO + T. triandra 300 mg/kg, and BLCCAO + T. triandra 600 mg/kg. Cerebral ischemia/reperfusion was induced by three minutes of bilateral common carotid artery occlusion (BLCCAO) followed by 18 days of reperfusion. Leaf extract was administered orally 24 hours after arterial occlusion and continued for 18 consecutive days. Cognitive abilities were evaluated using the Morris water maze. Histological analysis was conducted in the dorsal hippocampus subregions CA1, CA3, and DG and white matter regions (the corpus callosum, internal capsule, and optic tract) using 0.1 % cresyl violet and 0.1% Luxol fast blue staining. RESULTS: Results showed that T. triandra leaf extract at the doses of 300 and 600 mg/kg significantly enhanced spatial learning, and learning flexibility, and prevented neuronal death in the DG of mice following ischemia/reperfusion. CONCLUSION: T. triandra leaf extract enhanced spatial learning, and learning flexibility, and prevented DG neuronal death in a mice model of cerebral ischemia/reperfusion.

Reproductive toxicity of Momordica charantia ethanol seed extracts in male rats.

BACKGROUND: Momordica charantia (M. charantia) seed has been supposed to have an antifertility property but mechanisms underlying the infertility effect have not been investigated. OBJECTIVE: We investigated the antifertility effect of M. charantia ethanol seed extracts on reproductive toxicology and seminal and plasma testosterone in male Wistar rats. MATERIALS AND METHODS: The control group (I) was provided daily 1 ml dimethylsulfoxide (DMSO) and the experimental groups II and III were given daily 400 and 800 mg dry matter/kg body weight of the extracts dissolved in 1 ml DMSO via the esophageal route. All groups were administered for 42 days (day 42). Changes in body weight, fertility, reproductive characteristics, testicular histopathology and levels of seminal and plasma testosterone among three groups were compared. RESULTS: On day 42, the extracts caused antifertility (p=0.001). The extracts demonstrated significant reductions in diameters of seminiferous tubules and epididymides, spermatid density, daily sperm production and caudal epididymal spermatozoa, sperm motility and viability (p=0.046). Pathological changes in seminiferous tubules revealed atrophy, desquamation, pyknosis nucleus and multinucleated giant cell. Plasma cells were evident in three parts of epididymides of rats treated with high dose of the extract. Furthermore, the high dose of the extract suppressed seminal testosterone level (p=0.001) and plasma testosterone level (p=0.002). CONCLUSION: Our data showed that high dose of M. Charantia seed extracts caused infertility in male rats. The interruption in their fertility was probably attributed to the direct toxic to seminiferous tubules, epididymis and the lowered testosterone level which might impact on sperm parameters.