Impairment In Male Rats Research Articles

Gene network analysis combined with preclinical studies to identify and elucidate the mechanism of action of novel irreversible Keap1 inhibitor for Parkinson's disease.

The cysteine residues of Keap1 such as C151, C273, and C288 are critical for its repressor activity on Nrf2. However, to date, no molecules have been identified to covalently modify all three cysteine residues for Nrf2 activation. Hence, in this study, our goal is to discover new Keap1 covalent inhibitors that can undergo a Michael addition with all three cysteine residues. The Keap1's intervening region was modeled using Modeller v10.4. Covalent docking and binding free energy were calculated using CovDock. Molecular dynamics (MD) was performed using Desmond. Various in-vitro assays were carried out to confirm the neuroprotective effects of the hit molecule in 6-OHDA-treated SH-SY5Y cells. Further, the best hit was evaluated in vivo for its ability to improve rotenone-induced postural instability and cognitive impairment in male rats. Finally, network pharmacology was used to summarize the complete molecular mechanism of the hit molecule. Chalcone and plumbagin were found to form the necessary covalent bonds with all three cysteine residues. However, MD analysis indicated that the binding of plumbagin is more stable than chalcone. Plumbagin displayed neuroprotective effects in 6-OHDA-treated SH-SY5Y cells at concentrations 0.01 and 0.1 μM. Plumbagin at 0.1 µM had positive effects on reactive oxygen species formation and glutathione levels. Plumbagin also improved postural instability and cognitive impairment in rotenone-treated male rats. Our network analysis indicated that plumbagin could also improve dopamine signaling. Additionally, plumbagin could exhibit anti-oxidant and anti-inflammatory activity through the activation of Nrf2. Cumulatively, our study suggests that plumbagin is a novel Keap1 covalent inhibitor for Nrf2-mediated neuroprotection in PD.

Sodium nitroprusside restored lipopolysaccharide-induced learning and memory impairment in male rats via attenuating inflammation and oxidative stress.

Inflammation and oxidative stress upset memory. We explored influence of sodium nitroprusside (SNP) on memory deficits resulted from lipopolysaccharide (LPS).Groups include control, LPS, LPS + SNP 1 mg/kg, LPS + SNP 2 mg/kg, and LPS + SNP 3 mg/kg. Morris water maze and passive avoidance tests and biochemical measurements were carried out.In Morris water maze, LPS prolonged time and distance for finding the platform. In probe trial, it diminished time spent and traveled distance in the target zone. Injection of 2 and 3 mg/kg of SNP overturned the effect of LPS. In passive avoidance task, LPS postponed entrance into darkroom and reduced time spent in light room and incremented time spent in darkroom in 3, 24, and 72 h after electrical shock. All three doses of SNP restored the effects of LPS. Biochemical experiments confirmed that LPS elevated interleukin-6 and malondialdehyde concentration and declined total thiol content and superoxide dismutase and catalase activity in the hippocampus and cortex tissues. SNP particularly at a 3 mg/kg dose ameliorated LPS effects on these parameters.SNP attenuated memory disabilities resulting from LPS through modifying inflammation and boosting antioxidant defense.

Evaluating the Protective Effects of Melatonin Against Chronic Iron Administration in Male Wistar Rats: a Comparative Analysis of Affective, Cognitive, and Oxidative Stress with EDTA Chelator.

Iron is the dominant metal in the brain and is distributed widely. However, it can lead to various neuropathological and neurobehavioral abnormalities as well as oxidative stress. On the other hand, melatonin, a pineal hormone, is known for its neuroprotective properties, as well as its ability to act as a natural chelator against oxidative stress. It has also been used as an antidepressant and anxiolytic. The study investigated the potential of melatonin and EDTA treatment to prevent anxiety, depressive behavior, and memory impairment in male rats induced by chronic iron administration, and its connection to oxidative stress regulation in the hippocampus and prefrontal cortex. The rats were divided into six groups and intraperitoneally injected for 8weeks with NaCl solution (control), iron sulfate (1mg/kg), melatonin (4mg/kg), EDTA (4mg/kg), 1mg/kg of iron + 4mg/kg of melatonin, or 1mg/kg of iron + 4mg/kg of EDTA. In this study, we performed a neurobehavioral assessment and biochemical determinations of oxidative stress levels in the hippocampus and prefrontal cortex of each animal. The results indicate that chronic exposure to iron sulfate induced anxiety-like depressive behavior, and cognitive impairment also increased the levels of lipid peroxidation and nitric oxide, and reduced the activity of catalase in the hippocampus and prefrontal cortex in male Wistar rats, suggesting the induction of oxidative stress. In contrast, these alterations were reversed by melatonin better than EDTA. The results of this study show that melatonin protects against the neurobehavioral changes caused by iron, which may be associated with decreasing oxidative stress in the hippocampus and prefrontal cortex.

Icariin rescues developmental BPA exposure induced spatial memory deficits in rats

Bisphenol A (BPA) has been implicated in cognitive impairment. Icariin is the main active ingredient extracted from Epimedium Herb with protective function of nervous system. However, the potential therapeutic effects of Icariin on spatial memory deficits induced by developmental BPA exposure in Sprague-Dawley rats have not been investigated. This study investigated the therapeutic effect of Icariin (10 mg/kg/day, from postnatal day (PND) 21 to PND 60 by gavage) on spatial memory deficits in rat induced by developmental BPA exposure (1 mg/kg/day, from embryonic to PND 60), demonstrating that Icariin can markedly improve spatial memory in BPA-exposed rat. Furthermore, intra-gastric administration of Icariin could attenuate abnormal hippocampal cell dispersion and loss, improved the dendritic spine density and Nissl bodies. Moreover, Icariin reversed BPA induced reduction of frequency of miniature excitatory postsynaptic currents(mEPSC) and decrease of Vesicular glutamate transporter 1(VGlut1). Collectively, Icariin could effectively rescue BPA-induced spatial memory impairment in male rats by preventing cell loss and reduction of dendritic spines in the hippocampus. In addition, we also found that VGlut1 is a critical target in the repair of BPA-induced spatial memory by Icariin. Thus, Icariin may be a promising therapeutic agent to attenuate BPA-induced spatial memory deficits.

Zinc Ameliorates Tripterygium Glycosides-Induced Reproductive Impairment in Male Rats by Regulating Zinc Homeostasis and Expression of Oxidative Stress-Related Genes.

Tripterygium glycosides (TG) can seriously damage male reproductive function, and the reproductive system is difficult to restore after stopping the administration of TG in male rats. Zinc (Zn) is one of the most important trace elements in the human body and plays an important role in maintaining male fertility. The aim of this study was to investigate whether zinc supplementation could improve the testicular reproductive damage induced by TG toxicity in rats and to investigate its mechanism of action. The results showed that zinc sulfate (ZnSO4) could improve testicular tissue structure and semen parameters, promote testosterone synthesis, increase zinc-containing enzyme activity, increase zinc concentration in serum and testicular tissues, and maintain zinc homeostasis in male rats induced by TG toxicity. Zinc supplementation activated relevant signalling molecules in the KEAP1-NRF2/ARE pathway and alleviated TG-induced oxidative stress. Therefore, this study concluded that zinc supplementation could improve reproductive damage by regulating zinc homeostasis and the expression of genes related to oxidative stress.

Rivastigmine ameliorates botulinum-induced hippocampal damage and spatial memory impairment in male rats

Botulinum toxin (Botox) is widely used in beauty industry and its long-term consequences can be a matter of concern. The hippocampal cholinergic system plays a significant role in memory and learning that could be affected by Botulinum toxin. However, to date, the effect of Botox on memory system has been controversial. This survey aimed to examine the effects of Botox on spatial memory, and biochemical and histological parameters of the hippocampus in male rats by using Rivastigmine (R) as a cholinesterase inhibitor that is more selective for the central nervous system (CNS). Thirty-five male Wistar rats (200–250 g) were distributed into seven groups: Sham, Botox A (3, 6, and 15 IU intramascularly) and Botox A (3, 6, and 15 IU) plus Rivastigmine (1 mg/kg intraperitoneally). Spatial memory was assessed in the Morris Water Maze (MWM) 4 weeks later. Moreover, the hippocampal tissue was removed for histopathological and biochemical analyses. Botox significantly impaired memory performance in MWM by increasing escape latency and swim distance and decreasing the time spent in the target zone. Furthermore, in the Botox groups, the level of acetylcholine decreased, while the level of the acetylcholinesterase enzyme increased significantly in the hippocampus. Also, local lesions were observed in the form of degeneration and loss of pyramidal neurons, as well as a decrease in the volume and shrinkage of the cell body and an increase in microglia in the damaged area. Rivastigmine administration alleviated biochemical and histological parameters and partially ameliorated Botox-induced impairments.In summary, rivastigmine could be a suitable protective approach for side effects of Botox in the hippocampus.

Comparative effects of the alcoholic extract of Terminalia chebula and crocin on stress‑induced anxiety‑like behavior and memory impairment in male rats.

Crocin and Terminalia chebula (T. chebula) were proven to have neuroprotective effects. In this study, we evaluated the preventive effects of crocin and alcoholic extract of the T. chebula alone and in combination to examine their efficacy against chronic restraint stress (CRS)‑induced cognitive impairment, anxiety‑like behaviors, hippocampal synaptic plasticity deficit as well as neuronal arborization damage in the hippocampal CA1 neurons. Over 14 consecutive days, animals received crocin, T. chebula, or their combination (5 min before CRS). The elevated plus‑maze results showed that crocin and T. chebula alone and in combination treatment significantly increased the time spent in open arms, percentage of open arm entries, and head dipping as compared with the CRS group. Barnes maze results showed that administration of crocin and T. chebula alone and their combination significantly improves spatial memory indicators such as distance traveled, latency time to achieving the target hole, and the number of errors when compared to the CRS group. These learning deficits in CRS animals correlated with a reduction of long-term potentiation (LTP) in hippocampal CA1 synapses, which both T. chebula and crocin treatment improved field excitatory postsynaptic potentials (fEPSP) amplitude and fEPSP slope reduction induced by CRS. Golgi‑Cox staining showed that T. chebula and crocin treatment increased the number of dendrites and soma arbors in the CA1 neurons compared with the CRS group. Our results suggest that both T. chebula and crocin attenuated CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons. We found no significant difference between single treatments of T. chebula or crocin and their combination in protecting CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons.

A comparative study of scopolamine, D-Galactose and AlCl3-induced Alzheimer’s like disease by enhancing hippocampal neurodegeneration and memory impairment in male rats

A comparative study of scopolamine, D-Galactose and AlCl3-induced Alzheimer’s like disease by enhancing hippocampal neurodegeneration and memory impairment in male rats

Free-L-Cysteine improves corticosterone-induced behavioral deficits, oxidative stress and neurotransmission in rats.

L-Cysteine (L-Cys) is a semi-essential amino acid. It serves as a substrate for enzyme cystathionine-β-synthase in the central nervous system (CNS). L-Cys showed various antioxidant characteristics. Though, studies on the effect of free L-Cys administration to evaluate the CNS functioning is very limited. Therefore, we assessed the effects of L-Cys on corticosterone (CORT) induced oxidative stress, behavioral deficits and memory impairment in male rats. L-Cys (150mg/kg/ml) administered to vehicle and CORT (20mg/kg/ml) treated rats orally for 28days. Behavioral activities were conducted after treatment period. Subsequently, rats were sacrificed, blood and brain were removed. Hippocampus was isolated from brain and then hippocampus and plasma were collected for oxidative, biochemical and neurochemical analysis. Results showed that repeated treatment of L-Cys produced antidepressant, anxiolytic and memory-improving effects which may be ascribed to the enhanced antioxidant profile, normalized cholinergic, serotonergic neurotransmission in brain (hippocampus) following CORT administration. Increased plasma CORT by CORT administration was also normalized by L-Cys. The current study concluded that administration of free L-Cys improved the behavioral, biochemical, neurochemical and redox status of CNS. Hence, L-Cys could be protective therapeutic modulator against stress induced neurological ailments.

Comparison of the effect of vitamin C and selenium nanoparticles on gentamicin-induced renal impairment in male rats: a biochemical, molecular and histological study

Renal failure caused by gentamicin is mainly mediated through oxidative damage, inflammation, and apoptosis. Hence, vitamin C and selenium, which have antioxidant, anti-inflammatory, and anti-apoptotic properties, and their nanoparticle forms, which have recently received attention, may reduce gentamicin-induced side effects. Therefore, the aim of this study was to investigate the therapeutic effects of vitamin C and selenium, and their nanoparticles on gentamicin-induced renal damage in male rats. 128 adult male Wistar rats were randomly divided into equal sixteen controlled and treated groups. Serum levels of uric acid, blood urea nitrogen, urea, and creatinine were measured. Renal levels of oxidative parameters such as MDA, SOD, and CAT and inflammatory parameters including IL-1β, and TNF-α were measured. Renal expression of Nrf2, NF-κB, Bcl-2, caspase-3, BAX and mTORc1 was also evaluated. The results showed that gentamicin causes oxidative damage, inflammation, apoptosis and disruption of autophagy in kidney tissue in a dose-dependent manner. However, treatment with vitamin C, selenium and their nanoparticles could significantly improve these effects. Also, the results showed that the inflammatory and oxidative parameters and the expression of genes involved in them and apoptosis in the gentamicin groups treated with vitamin C nanoparticles and selenium nanoparticles reduced significantly compared to those treated with vitamin C and selenium. It can be concluded that vitamin C, selenium and their nanoparticles can improve gentamicin-induced kidney damage by inhibiting oxidative damage, inflammation and apoptosis-induced by autophagy, and can be a good option for kidney damage caused by gentamicin or as an adjunctive treatment to reduce its side effects.

MicroRNA modulation is a potential molecular mechanism for neuroprotective effects of intranasal insulin administration in amyloid βeta oligomer induced Alzheimer's like rat model.

Substantial evidence indicates that imbalance in the expression of miR-132-3p, miR-181b-5p, miR-125b-5p, miR-26a-5p, miR-124-3p, miR-146a-5p, miR-29a-3p, and miR-30a-5p in the AD brain are associated with amyloid-beta (Aβ) aggregation, tau pathology, neuroinflammation, and synaptic dysfunction, the major pathological hallmarks of Alzheimer's disease)AD(. Several studies have reported that intranasal insulin administration ameliorates memory in AD patients and animal models. However, the underlying molecular mechanisms are not yet completely elucidated. Therefore, the aim of this study was to determine whether insulin is involved in regulating the expression of AD-related microRNAs. Pursuing this objective, we first investigated the therapeutic effect of intranasal insulin on Aβ oligomer (AβO)-induced memory impairment in male rats using the Morris water maze task. Then, molecular and histological changes in response to AβO and/or insulin time course were assessed in the extracted hippocampi on days 1, 14, and 21 of the study using congo red staining, western blot and quantitative real-time PCR analyses. We observed memory impairment, Aβ aggregation, tau hyper-phosphorylation, neuroinflammation, insulin signaling dys-regulation, and down-regulation of miR-26a, miR-124, miR-29a, miR-181b, miR-125b, miR-132, and miR-146a in the hippocampus of AβO-exposed rats 21days after AβO injection. Intranasal insulin treatment ameliorated memory impairment and concomitantly increased miR-132, miR-181b, and miR-125b expression, attenuated tau phosphorylation levels, Aβ aggregation, and neuroinflammation, and regulated the insulin signaling as well. In conclusion, our study suggest that the neuroprotective effects of insulin on memory observed in AD-like rats could be partially due to the restoration of miR-132, miR-181b, and miR-125b expression in the brain.

Lutein Attenuates Cyclosporin-induced Testicular Impairment in Male Rats through Modulation of Androgenic Hormones and Enzymes

Background: Male reproductive toxicity has been linked to cyclosporine, a commonly used immunosuppressive drug for the prevention of organ rejection in patients undergoing renal transplant. The goal of this study was to elucidate how lutein protects male testicles from cyclosporine-induced damage. Methods: Thirty adult male Wistar rats were randomly allotted to five groups, each with six animals. Rats in groups 1 and 2 were given saline (2 mL/kg/day p.o) and corn oil (2 mL/day p.o) respectively. Rats in groups 3 and 4 were given lutein (40 mg/kg/day p.o) and cyclosporine (40 mg/kg/p.o./day), while rats in group 5 were given a combination of cyclosporine (40 mg/kg/day p.o) and lutein (40 mg/kg/day p.o). At the end of the fourth week, sperm indices, serum hormones, testicular steroidogenic enzymes [3 and 17 beta-hydroxysteroid dehydrogenases (3ß-HSD and 17ß-HSD)] and enzyme markers of spermatogenesis [lactate dehydrogenase (LDH-X), sorbitol dehydrogenase (SDH), gamma glutamyl transferase (?-GT), acid phosphatase (ACP) and alkaline phosphatase (ALP)] were assayed. The testis of each rat was also investigated for histopathological abnormalities and germ cell count. Results: Lutein attenuated cyclosporine-induced sperm impairment. In rats treated with cyclosporine, lutein reduced LDH-X, SDH, ACP, ?-GT; raised LH, FSH, testosterone, 3ß-HSD, 17ß-HSD, ALP levels, and improved spermatogenesis. Conclusion: These results suggest that lutein attenuates cyclosporine-induced testicular impairment through modulation of androgenic hormones and enzymes.

The therapeutic effects of distinct exercise types on metabolic syndrome-induced reproductive system impairment in male rats: Potential contribution of mitochondria-related genes.

A sedentary lifestyle and high fructose dietary habits cause diseases, such as metabolic syndrome (MS). The study was aimed to investigate the potential ameliorative effects of different exercise interventions on high fructose-induced MS-mediated reproductive system disruption of male rats. Rats were divided into four groups (n=6): Control, MS, MS+aerobic exercise (AE) and MS+anaerobic exercise (ANE). MS was induced by using tap water containing 30% fructose for 8weeks. After the induction of MS, AE/ANE implementations were started for 6weeks. Testis tissue and serum samples of rats were stored for biochemical and molecular analyses. Serum total antioxidant status level increased in the MS+AE group compared to all groups. Also, serum total oxidant status level, which increased by MS, decreased with AE, but not altered with ANE. Moreover, MS markedly decreased serum luteinizing hormone, but not changed the follicle-stimulating hormone. However, serum hormone levels were similar to the control group in both MS+AE and MS+ANE groups. MS upregulated mitochondria-related genes' mRNA expressions (MFN2, PGC1A, PPARG, PARP2 and TXNL4B). These increases, except for PPARG, were normalized with both exercise types. These results revealed that mitochondria-related genes may have a crucial role in MS-mediated male reproductive impairment and therapeutic effects of exercises.

Effects of Aminoguanidine on Apoptosis in the Hippocampus and Memory Disorder in a Rat Model of Alzheimer’s Disease

Background: Memory loss is the main disorder accompanied by Alzheimer's disease (AD). Objectives: We aimed to investigate the protective effects of aminoguanidine (Amg) on cell apoptosis in the hippocampal CA1 region and memory impairment in male rats received scopolamine (Scop). Methods: Thirty male Wistar rats (200 - 250 g) were randomly divided into the three groups of saline-saline group, Scop + saline, and Scop + Amg groups. The rats received intraperitoneal injection of Scop (3 mg/kg) for seven days, and subsequently, 100 mg/kg of Amg or normal saline were intraperitoneally administrated for 14 consecutive days. The Morris water maze test was used to study memory deficits. Finally, the animals were anesthetized, hippocampi were quickly removed, histological study was performed, and hippocampal cell apoptosis was evaluated by the cresyl violet staining and the terminal deoxynucleotidyl transferase dUTP nick end labeling test, respectively. Results: Scop injection resulted in reduced pyramidal cells and increased cell apoptosis in the hippocampal CA1 area, and impaired spatial learning and memory. The administration of Amg significantly improved memory and improved the density of pyramidal cells in the hippocampal CA1 area of the rats (P < 0.01). Also, the number of apoptotic cells in the CA1 region of the hippocampus in the Scop + Amg group decreased compared to the Scop + saline group (P < 0.05). Conclusions: These data demonstrate that the intraperitoneal injection of Amg declined the number of apoptotic cells in the CA1 area of the hippocampus and improved memory impairment in the Scop-induced rat model of AD. It is suggested that Amg may have protective effects against AD.

The Effect of Spironolactone on β-amyloid-Induced Memory Impairment in Male Rats: The Role of Microglial Inhibition.

Purpose: Neuroinflammation was indicated in the pathophysiology of Alzheimer’s disease (AD). Previous reports have also signified that spironolactone has anti-inflammatory effects. Therefore, the aim of this study was to assess the modulatory effects of spironolactone on neuroinflammation and memory loss in a rat model of AD. Methods: The β-amyloid protein fragment 25-35 (Aβ) was injected in the dorsal hippocampus (5 μg/2.5 μL each side) of male Sprague-Dawley rats for four consecutive days to induce memory impairment. Animals have intraperitoneally received spironolactone (10, 25, or 50 mg/kg, N = 6/ group) or vehicle for 14 days. The passive inhibitory avoidance and the novel recognition tests were used for memory evaluation. Neuroinflammation was assessed by measuring the level of Iba1 protein, a marker of microglial activation, using western immunoblotting. Results: Different doses of spironolactone showed no significant changes in latency times and discriminations ratios in passive inhibitory avoidance and novel recognition tests, respectively, as compared to vehicle. However, spironolactone-treated groups showed significantly lower Iba1 protein levels in comparison to the vehicle-treated group (P < 0.01). Conclusion: Spironolactone had a modulatory effect on neuroinflammation through a repressive effect on microglial activation with no valuable effect on memory improvement in a rat model of AD. The findings of this study suggest that Aβ-induced memory loss may not be directly linked to microglial activation. Spironolactone may be a potential candidate to be examined in other neuroinflammatory disorders.

Spathodea companulata (African tulip tree) stem and root barks extracts ameliorated N-nitroso diethylamine induced hepatic impairment in male rats

Spathodea campanulata Beauv. is an important plant widely used in traditional medicine for the treatment of hepatic disease. In the present study, we evaluate the phytochemical composition and hepatoprotective potential effect of the stem and root bark extracts of Spathodea companulata on dimethylnitrosamine (DEN) induced hepatic impairment in albino rats. Phytochemical compositions were analyzed using standard protocols. Forty-five male rats were grouped into 9 (A-I) of 5 rats each. Groups A-F were treated with stem bark extract, root bark extract, quercetin, DEN + stem bark extract, DEN + root bark extract, DEN + quercetin respectively while groups G-1 serve as control groups and were treated with corn oil only (Vehicle control), DEN only (Toxicant control), and distilled water (normal control) respectively. DEN was given at 25 mg/kg b.w., i.p on a weekly basis while all treatments were administered at 100 mg/kg BW orally for 60 days. Serum transaminase activities, body weight, and liver body weight ratio were evaluated. Results revealed the presence of alkaloids, cardiac glycoside, saponins, anthraquinone, steroids, and flavonoids in stem bark extract of Spathodea companulata, while the root bark contains cardiac glycoside, saponins, anthraquinonoid, steroids, and flavonoid. The DEN non-treated rat exhibited significant (p&lt;0.05) weight loss and increase serum alanine transaminase (ALT) and aspartate transaminase (AST) activities when compared with the normal control. Treatment with stem and root bark extracts of Spathodea companulata significantly ameliorated the toxicant induce alterations in the transaminase activity and body weight loss when compared with the DEN nontreated rats. In conclusion, this study provides scientific validation of the use of this plant in traditional medicine for the management of hepatic disorders

Effect of vitamin E on cisplatin-induced memory impairment in male rats.

Neurotoxicity is an adverse effect caused by cisplatin due to inflammation and oxidative stress in the central nervous system. The present study aimed to assess the effects of vitamin E injection on the learning and memory of rats with cisplatin-induced cognitive impairment. Male rats were administered with cisplatin (2 mg/kg/7 day; intraperitoneally [i i.p.]) and/or vitamin E (200 mg/kg/7 day; i.p.) for 1 week, and the control group received saline solution. Spatial memory was evaluated using Morris water maze (MWM). In addition, the hippocampal concentrations of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) were measured using biochemical methods. According to the findings, cisplatin significantly increased the escape latency, while decreasing the time spent and travelled pathway in the target quadrant on the final trial day compared to the control group. Furthermore, pre-treatment with vitamin E significantly reversed all the results in the spatial memory test. The biochemical data indicated that vitamin E could decrease MDA activity and increase thiol and SOD activity compared to the control group. According to the results, vitamin E could improve cisplatin-induced memory impairment possibly through affecting the hippocampal oxidative status.

The beneficial effect of oyster peptides and oyster powder on cyclophosphamide-induced reproductive impairment in male rats: A comparative study.

This study aimed to evaluate the effect of oyster peptides and oyster powder on the procreative capacity of rats displaying reproductive dysfunction induced by cyclophosphamide (CTX). The amino acid composition and relative molecular mass of the oyster peptides and oyster powder were detected using an automatic amino acid analyzer and high-performance liquid chromatography (HPLC). After 5 d of exposure to CTX and six weeks of oyster peptide and oyster powder treatment, the biochemical serum indexes of the rats, the expression of related genes and proteins in the testes, as well as the antioxidant status and pathological state of the testes and kidneys were examined. The results showed that oyster peptides could effectively improve the biochemical blood indexes of rats, and increase the level of androgen in the blood, while improving the pathological state and oxidative stress state of the kidneys and testes, therefore, exhibiting a beneficial effect on reproductive injury. PRACTICAL APPLICATIONS: This study examined the activity of oyster peptides and their ability to enhance the procreative capacity of rats with reproductive dysfunction induced by CTX while analyzing the amino acid composition and relative molecular mass of the oyster peptides. The results of this experiment provided a preliminary theoretical basis for the development of new functional foods using oyster peptides.

Inhibition of rat brain and human red cell acetylcholinesterase by thiocarbamate herbicides.

Thiocarbamates are a major class of herbicides that were used extensively in the agricultural industry. Toxicological evaluation showed molinate caused reproductive impairment in male rats, whilst others produced behavioural effects at high doses. Rats dosed with molinate either as a single large oral dose of 100mg/kg or as multiple doses of 50mg/kg for 7 days produced inhibition of brain acetylcholinesterase (AChE). Molinate and other thiocarbamate herbicides undergo metabolism to form sulphoxides that can carbamoylate thiol's such as glutathione and proteins. We have chemically synthesised the sulphoxide and sulphone metabolites of six thiocarbamate herbicides and examined their ability to inhibit rat brain and human red cell AChE in vitro. Parent thiocarbamates were inactive, whilst the sulphoxides produced inhibition with IC50's in the 1-10mM range, the sulphone metabolites were the most active with IC50's for molinate, pebulate, EPTC and vernolate in the μM range. Inhibition was both time- and dose-dependent with biomolecular rate constants for the inhibition of the human red cell enzyme of 0.3×102 and 2.0×102M-1min-1 for molinate sulphoxide and sulphone, respectively. No recovery of enzyme activity, with either enzyme, was seen following dilution of the inhibitor to a concentration that does not inhibit the enzyme for up to 24h at 25°C at pH7.4. The metabolites of these thiocarbamate herbicides are rather poor inhibitors of AChE when compared to the organophosphorus ester, paraoxon or the monomethylcarbamate, eserine. Unlike eserine the inhibition produced by the thiocarbamates is irreversible.

Antidiabetic and anti-inflammatory effects of two Fabaceae extracts against streptozotocin induced diabetic impairment in male rats

The present study aimed to investigate the antidiabetic and anti-inflammatory effects of Trifolium alexandrinum (TA) and Trifolium Pretense (TP) against streptozotocin induced diabetic impairment in male rats. Forty adult Wistar albino male rats were divided into four groups: Group 1, Control; Group 2, streptozotocin (STZ); Group 3, STZ + TA –treated group and Group 4, STZ + TP–treated group. TA and TP showed a significant reduction in the blood glucose, glycosylated hemoglobin (Hb A1C) levels and elevation in insulin and C-peptide. They restored the glycogen content of liver and skeletal muscle, also showed improvements in the activities of α-amylase, carbohydrate metabolic enzymes, lipase and lipid profile. Treatment with TA and TP extracts resulted in an improvement of the oxidative parameters and enhancement in the antioxidant enzymes in the pancreas and liver. While, pancreatic TNF-α, IL-1β, IL-6, NO, iNos and caspase-3 levels were significantly reduced with the treatment of TA and TP extracts. Administration of TA and TP extracts to diabetic rats revealed elevation in the GLUT4 levels of the skeletal muscle and pancreas. They caused up regulation in pancreatic GLUT2 gene expression. TA and TP extracts showed signs of regeneration of β-cells and improvement in the pancreatic tissue. It could be concluded that TA and TP extracts possess antioxidant and hypoglycemic potential resulting in reduction of the elevated oxidative stress and pro-inflammatory cytokines.