Protective effects of Aloe vera gel on cisplatin-induced oxidative stress, apoptosis and neurons structure in rat hippocampus.

Cisplatin (CP) as an important chemotherapeutic drug is used for the treatment of various malignancies; but it has some side effects on central nervous system, in particular hippocampus. The present study was aimed to determine the protective effects of Aloe vera (AV) gel on CP-induced oxidative stress, apoptosis and neurons structure changes in the hippocampus of rats. Forty-eight rats were divided into six groups including control, CP (5.00 mg kg-1 per week; intraperitoneally), CP + AV (400 mg kg-1 per day; orally), CP + metformin (200 mg kg-1 per day; orally), AV (400 mg kg-1 per day; orally) and metformin (200 mg kg-1 per day; orally). At the end of treatment, brain samples were obtained for analysis of apoptotic genes expression and anti-oxidant markers as well as histological study. The results showed that CP caused an increase in malondialdehyde level and a decrease in glutathione peroxidase, superoxide dismutase and catalase levels in CP group compared to control. The AV gel could diminish oxidative stress in the hippocampus of CP group and it resulted in down-regulation of Bax, caspase-3 and caspase-8 and up-regulation of Bcl-2 in CP group. It could ameliorate degenerative changes in hippocampus after exposure to CP. Our results showed that AV gel ameliorated oxidative stress, apoptosis and neuronal loss in the hippocampus of rats under CP treatment.

Chemical and Green ZnO nanoparticles ameliorated adverse effects of cisplatin on histological structure, antioxidant defense system and neurotrophins expression in rat hippocampus.

Cisplatin (CP) is a chemotherapy agent used in the treatment of cancer, but it has various side effects, in particular, neurotoxicity. Zinc oxide nanoparticles (ZnO NPs) are a potent antioxidant. However, there is limited knowledge about the protective effects of ZnO NPs against CP-induced hippocampal toxicity. The present study aimed to explore the potential protective effects of ZnO NPs against CP-induced oxidative stress, loss of neurotrophins support, and tissue damage in the hippocampus of the rats. Eighty adult male Wistar rats were dividing into ten groups including: control (Con), sham, ZnO Bulk (ZnB), chemical ZnO NPs (ChZnO NPs), Green ZnO NPs (GrZnO NPs), CP, CP + ZnB, CP + ChZnO NPs, CP + GrZnO NPs and CP + AE. CP was administrated (5 mg/kg/weekly) for four weeks, and animals were treated simultaneously with different forms of ZnO (5 mg/kg/day). At the end of the experiment, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), changes of reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio, histological changes, expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) genes were assessed in the hippocampus. The results revealed that a decrease in BDNF and NGF mRNA expression, GSH concentration and GSH/GSSG ratio, increasing of GSSG and MDA levels, and neuronal loss in the CP-treated rats were reversed following the administration of different forms of ZnO, especially Gr ZnO NPs and ch ZnO NPs. Co-administration of ZnO NPs to CP-treated rats restored the suppressive effects of CP on activities of antioxidant enzymes (SOD, GPX, CAT). The results showed that in most of the evaluated factors, Gr ZnO NPs showed a greater protective effect than other forms of ZnO. The results suggest that ZnO NPs, in particular Green ZnO NPs (GrZnO NPs) had more potential protective effects against CP-induced oxidative stress, inadequate support neurotrophin and tissue damage in rat hippocampus.

Protective Effect of Aloe vera Gel against Cisplatin-Induced Testicular Damage, Sperm Alteration and Oxidative stress in Rats.

BACKGROUND: Cisplatin (CIS) is an effective antineoplas tic drug that is used to treat various types of cancers. However, it causes side effects on the male reproductive sys tem. The present s tudy aimed to inves tigate the possible protective effects of Aloe vera (AL) gel (known as an antioxidant plant) on CIS-induced changes in rat sperm parameters, tes ticular s tructure, and oxidative s tress markers. MATERIALS AND METHODS: In this experimental study, forty-eight adult male rats were divided into 6 groups including: control, CIS, AL, metformin (MET), CIS+AL, and CIS+MET. CIS was used intraperitoneally at a dose of 5 mg/kg on days 7, 14, 21, and 28 of the experiment. AL gel (400 mg/kg per day) and MET (200 mg/kg per day) were administered orally for 35 days (started one week before the beginning of the experiment). Testes weight and dimensions, and morphometrical and histological alterations, activities of antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GPx), serum testosterone concentration, lipid peroxidation level, and sperm parameters were examined. RESULTS: CIS caused a significant decrease (P<0.05) in relative weight and dimension of the testis, germinal epithelium thickness and diameter of seminiferoustubules, the numbers of testicular cells, and spermatogenesis indexes. The malondialdehyde (MDA) levels increased and antioxidant enzymes activities decreased in the CIS group compared to the control group (P<0.05). Additionally, sperm parameters (concentration, viability, motility, and normal morphology), and testosterone levels reduced significantly in CIS-treated rats (P<0.05). Also, CIS induced histopathological damages including disorganization, desquamation, atrophy, and vacuolation in the testis. However, administration of AL gel to CIS-treated rats attenuated the CIS-induced alterations, mitigated testicular oxidative stress and increased testosterone concentration. CONCLUSION: The results suggest that AL as a potential antioxidant plant and due to free radicals scavenging activities, has a protective effect against CIS-induced testicular alterations.

Protective effects of green and chemical zinc oxide nanoparticles on testis histology, sperm parameters, oxidative stress markers and androgen production in rats treated with cisplatin.

Cancer treatment with cisplatin (CP) is associated with adverse side effects on male reproductive tissues. Although beneficial effects of zinc oxide nanoparticles (ZnO NPs) in cancer therapy have received considerable attention, data related to the protective effects of green ZnO NPs against CP-induced male reproductive dysfunctions are limited. Forty-five rats were divided into 9 groups including G1 (control), G2 (sham), G3 (ZnO bulk), G4 (green ZnO NPs), G5 (chemical ZnO NPs), G6 (CP), G7 (CP + ZnO bulk), G8 (CP + green ZnO NPs), and G9 (CP + chemical ZnO NPs). CP was administrated (5 mg/kg/week) for 4 weeks, and animals were simultaneously treated with different forms of ZnO (5 mg/kg/day). Testis histology, sperm parameters, oxidative stress markers, testosterone concentration, and expression of genes related in steroidogenesis were analyzed in different experimental groups. Testis tissue damage and epididymal sperm disorders induced by CP attenuated when animals were treated with different forms of ZnO, especially green ZnO NPs. Decreased testosterone concentration and increased MDA level in CP-treated rats were reversed following administration different forms of ZnO, especially green and chemical ZnO NPs. Co-administration of ZnO NPs to CP-treated rats restored the suppressive effects of CP on activities of antioxidant enzymes (SOD, GPX, CAT) and the transcription of the STAR gene. None of the ZnO forms had a significant regulatory effect on the expression of CYP11A1 in CP-treated rats. The results showed that in most of the evaluated factors, green ZnO NPs showed a greater protective effect than other forms of ZnO.

Metformin attenuates cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells.

Metformin is widely used as an oral hypoglycemic drug in the management of type 2 diabetes mellitus. This study evaluated the possible protective effects of metformin against cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells. Two different doses of metformin (50 and 100 mg/kg b.w.) were administered orally to experimental animals for seven consecutive days. On the seventh day, the rats were exposed to cisplatin (5 mg/kg, i.p.) 1 h after the last oral metformin administration. Rats in the control group were treated orally with 10 ml/kg PBS for 7 consecutive days and a single intraperitoneal injection of saline (0.9%) on the 7th day. The antagonistic effects of metformin against cisplatin were evaluated using micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis, and flow cytometry. Treatment with 50 and 100 mg/kg metformin before cisplatin injection produced a significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after cisplatin treatment with a corresponding increase in the PCE/(PCE + NCE) ratio. Moreover, metformin markedly elevated the levels of both red and white blood cells in peripheral blood and decreased the percentage of apoptotic cells and the ROS level in bone marrow cells of rats treated with cisplatin. The data suggest that metformin has potential chemoprotective properties in rat bone marrow after cisplatin treatment, which support its candidature as a potential chemoprotective agent for cancer patients undergoing chemotherapy.

Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele.

Since autophagy was suspected to occur in the pathological situation of varicocele (VCL), we have attempted to confirm it here using a surgical model of varicocele-induced rats. Thirty Wistar rats were divided into three groups (varicocele/sham/control) and analyzed two months after the induction of varicocele. Testicular tissue sections and epididymal mature sperm were then monitored for classic features of varicocele, including disturbance of spermatogenesis, impaired testicular carbohydrate and lipid homeostasis, decreased sperm count, increased sperm nuclear immaturity and DNA damage, oxidative stress, and lipid peroxidation. At the same time, we evaluated the Atg7 protein content and LC3-II/LC3-1 protein ratio in testis and mature sperm cells, two typical markers of early and late cellular autophagy, respectively. We report here that testis and mature sperm show higher signs of autophagy in the varicocele group than in the control and sham groups, probably to try to mitigate the consequences of VCL on the testis and germ cells.

Effect of Abelmoschus esculentus Powder on Ovarian Histology, Expression of Apoptotic Genes and Oxidative Stress in Diabetic Rats Fed with High Fat Diet.

Okra (A.esculentus) is an antidiabetic plant whose beneficial effect on ovarian dysfunction in diabetes condition has not been clarified. The present study was designed to examine the effect of Okra powder on serum oxidant/antioxidant status, ovarian structure, and expression of apoptotic/antiapoptotic related genes in ovary of experimentally induced high fat diet diabetic rats. Diabetes was induced by 5 weeks feeding of Wistar rats with high fat diet (HFD) and subsequent i.p injection of STZ (35 mg/kg). Diabetic animals (serum glucose above 250 mg/dL) were treated with Okra powder (200mg/kg) supplemented in diet or metformin (200mg/kg) for 30days. After 30 days of treatment, animals were euthanized and insulin resistance markers (insulin and glucose levels and HOMA-IR), ovarian expression of apoptotic/antiapoptotic genes (Bax, caspase3 and Bcl2) and serum oxidant/antioxidant levels (SOD, GPX and CAT activities and MDA level) were determined. The ovaries were also processed for histological study. Hyperglycemia and reduced body weight of diabetic rats were improved after administration of Okra for 30days. This effect was relatively similar to metformin. Okra resulted in reduction of follicular atresia in concomitant with down regulation of apoptotic related genes (Bax and caspase3) in ovary of diabetic rats. Okra could also diminished oxidative stress in diabetic rats by increasing of serum GPX and CAT activities and reducing the lipid peroxidation level. The results of the present study revealed that Okra powder could be useful intervention for improvement of ovaian dysfunction in diabetic rat by three probable mechanisms; attenuation of glucotoxicity, down regulation of ovarian apoptosis related genes and reduction of oxidative stress.

Okra (Abelmoscus esculentus) Improved Islets Structure, and Down-Regulated PPARs Gene Expression in Pancreas of High-Fat Diet and Streptozotocin-Induced Diabetic Rats.

OBJECTIVES: Okra (Abelmoschus esculentus) is a tropical vegetable that is rich in carbohydrates, fibers, proteins and natural antioxidants. The aim of the present study was to evaluate the effects of Okra powder on pancreatic islets and its action on the expression of PPAR-γ and PPAR-α genes in pancreas of high-fat diet (HFD) and streptozotocininduced diabetic rats. MATERIALS AND METHODS: In this experimental study, diabetes was induced by feeding HFD (60% fat) for 30 days followed by an injection of streptozotocin (STZ, 35 mg/kg). Okra powder (200 mg/kg) was given orally for 30 days after diabetes induction. At the end of the experiment, pancreas tissues were removed and stained by haematoxylin and Eozine and aldehyde fuchsin for determination of the number of ß-cells in pancreatic islets. Fasting blood sugar (FBS), Triglycerides (TG), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and insulin levels were measured in serum. Moreover, PPAR-γ and PPAR-α mRNAs expression were measured in pancreas using real time polymerase chain reaction (PCR) analysis. RESULTS: Okra supplementation significantly decreased the elevated levels of FBS, total cholesterol, and TG and attenuated homeostasis model assessment of basal insulin resistance (HOMA-IR) index in diabetic rats. The expression levels of PPAR-γ and PPAR-α genes that were elevated in diabetic rats, attenuated in okra-treated rats (P<0.05). Furthermore, okra improved the histological damages of pancreas including vacuolization and decreased ß-cells mass, in diabetic rats. CONCLUSIONS: Our findings confirmed the potential anti-hyperglycemic and hypolipidemic effects of Okra. These changes were associated with reduced pancreatic tissue damage. Down-regulation of PPARs genes in the pancreas of diabetic rats after treatment with okra, demonstrates that okra may improve glucose homeostasis and ß-cells impairment in diabetes through a PPAR-dependent mechanism.

The histological and histometrical effects of Urtica dioica extract on rat's prostate hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth of the prostate gland leads to impinge on the urethra with impairment in urinary function. Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2 received 10 mg kg(-1) testosterone subcutaneously, G3 received 50 mg kg(-1) nettle root extract orally, G4 received 50 mg kg(-1) nettle root extract orally and 10 mg kg(-1) testosterone, G5 received 10 mg kg(-1) almond oil (Almond oil was used as testosterone solvent) subcutaneously. After six weeks, volume and weight of each lobe were measured and samples were taken. The 5 to 6 µm thickness sections were made using paraffin embedding method and stained by hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and ratio of prostate to body weight were increased significantly in the testosterone. Histological and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle root could prevent from some of prostatic hyperplasia effects, so that percentage of folded alveoli in ventral lobe reduced insignificantly.

Effects of dietary vitamin E on mucosal maltase and alkaline phosphatase enzyme activities and on the amount of mucosal malonyldialdehyde in broiler chickens.

The effects of dietary vitamin E levels on mucosal maltase and alkaline phosphatase (ALP) enzyme activities and on the amount of mucosal malonyldialdehyde (MDA) in broiler chickens were studied in the present study. One hundred and eighty of male day old broiler chicks (Ross 308 strain) were randomly assigned into five groups, each with three replicates and 12 chicks in each replicate. Chickens in group A were fed corn-soy- based diet, while those in groups B, C, D and E were fed the same diet with 20, 60, 180, and 540 mg kg(-1) vitamin E supplement (d-alpha tocopherol), respectively. Six birds were randomly chosen from each group, and were euthanized on days 10, 21, 32, and 42 of age. One segment of small intestine outset was homogenized and mucosal ALP and maltase activity were measured. Moreover, mucosal lipid peroxidate amount was measured to reveal the impact of vitamin E on oxidative stress. Maltase activity was increased with the increase of vitamin E up to 60 mg kg(-1) of diet while with further levels, it was decreased. Addition of 60 mg kg(-1) of vitamin E to the diet significantly increased ALP enzyme activity (p ≤ 0.001). Addition of 540 mg kg(-1) of vitamin E supplement to the diet led to the minimum amount of MDA at 32 days of age. It may be concluded that supplementation of broiler's diet with 60 mg kg(-1) of vitamin E can increase mucosal maltase and ALP enzyme activity.

Maternal caffeine consumption has irreversible effects on reproductive parameters and fertility in male offspring rats.

OBJECTIVE: Concerns are growing about the decrease in male reproductive health. Caffeine is one of the popular nutrients that has been implicated as a risk factor for infertility. In the present study, we examined whether in utero and lactational exposure to caffeine affects the reproductive function of the offspring of rats. METHODS: Pregnant rats received caffeine via drinking water during gestation (26 and 45 mg/kg) and lactation (25 and 35 mg/kg). Body and reproductive organ weight, seminiferous tubule diameter, germinal epithelium height, sperm parameters, fertility rate, number of implantations, and testosterone level of the offspring were assessed from birth to adulthood. RESULTS: Significant dose-related decreases were observed in the body and reproductive organ weight, seminiferous tubule diameter, and germinal epithelium height of the offspring. Sperm density had declined significantly in offspring of the low-dose and high-dose groups, by 8.81% and 19.97%, respectively, by postnatal day 150. The number of viable fetuses had decreased significantly in females mated with male offspring of the high-dose group at postnatal days 60, 90, 120, and 150. There were also significant reductions in testosterone levels of high-dose group offspring from birth to postnatal day 150. CONCLUSION: It is concluded that maternal caffeine consumption impairs gonadal development and has long-term adverse effects on the reproductive efficiency of male offspring rats.