Mitochondria-Mediated Apoptosis Induced Testicular Dysfunction in Diabetic Rats: Ameliorative Effect of Resveratrol

Endocrinology ◽  
2021 ◽  
Vol 162 (4) ◽  
Author(s):  
Hamdy A A Aly

Abstract The molecular mechanism underlying diabetes-induced testicular damage has not been thoroughly elucidated. The present study was conducted to elucidate the role of mitochondria-mediated apoptosis in diabetes-induced testicular dysfunction in rats and to explore the ameliorative effect of resveratrol. Diabetes suppressed sperm count, motility, and viability and increased sperm abnormalities. It decreased serum testosterone level and testicular mitochondrial membrane potential. The level of Bax and caspase-3 and -9 activities were increased in the testicular cytosol, while the level of Bcl-2 was decreased. Diabetes increased the Bax/Bcl-2 ratio. The cytochrome C level was decreased in the mitochondrial fraction, while its level was increased in the cytosol, a result that was supported by the immunohistochemistry of cytochrome C. Diabetes resulted in deleterious alterations in the architecture of testicular tissue, suppressed antioxidant enzymes, and increased H2O2 production, protein carbonyl content, and lipid peroxidation. However, administration of resveratrol at a dose of 50 mg kg/day for 4 successive weeks post diabetic induction, successfully ameliorated the testicular dysfunction. In conclusion, these findings strongly reveal that diabetes induces testicular damage, at least in part, by inducing mitochondrial-mediated apoptosis and oxidative stress. Administration of resveratrol to diabetic rats improves the diabetes-induced testicular damage. These impacts could be mediated through resveratrol antioxidant and anti-apoptotic effects.

2019 ◽  
Vol 2 (2) ◽  
pp. 1-21 ◽  
Author(s):  
Elina Mitra ◽  
Bharati Bhattacharjee ◽  
Palash Kumar Pal ◽  
Arnab Kumar Ghosh ◽  
Sanatan Mishra ◽  
...  

Cadmium (Cd) is a notorious environmental pollutant known for its wide range of toxicities to organisms. Thus, the present study is designed to examine whether melatonin, a potent antioxidant, protects against Cd-induced oxidative damage in the heart, liver and kidney of rats. Cd treatment at a dose of 0.44 mg/kg for 15 days caused severe damage in all these organs. These included significantly increased activities of SGPT, SGOT, lactate dehydrogenase- 1 and 5 and ALP and levels of total lactate, creatinine, lipid peroxidation, protein carbonyl content and reduced glutathione while the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase along with mitochondrial pyruvate dehydrogenase, isocitrate dehydrogenase, α-keto glutarate dehydrogenase, succinate dehydrogenase, NADH-cytochrome-c-oxidoreductase and cytochrome-c-oxidase were significantly reduced by Cd. However, if melatonin was given orally 30 min before Cd injection, all these alterations induced by Cd were significantly preserved by melatonin. Histological observations also demonstrated that Cd exposure caused cellular lesions, promoting necrotic or apoptotic changes. Notably, all these changes were significantly protected by melatonin. The results suggest that melatonin is a beneficial molecule to ameliorate Cd-induced oxidative damage in the heart, liver and kidney tissues of rats with its powerful antioxidant capacity, heavy metal chelating activity and competition of binding sites with Cd to the GSH and catalase.


2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Nkosinathi David Cele ◽  
Nonhlakanipho Felicia Sangweni ◽  
Rebamang Anthony Mosa ◽  
Dambudzo Penduka ◽  
Geraldine Genevive Lazarus ◽  
...  

The traditional use of medicinal plants in the management of sexual dysfunctions has a long history. This study investigated testicular dysfunction ameliorative effect of the methanolic roots extracts of Maytenus procumbens and Ozoroa paniculosa in a butanol-induced testicular dysfunction rat model. The rats in respective experimental groups were orally administered with the extract at 50 and 250 mg/kg bw, daily for 28 days. The cytotoxicity of the extracts was evaluated against HEK293, MCF-7, and HT29 cell lines. The extracts exhibited moderate (LC50 30.3–330.2 μg/mL) to weak (LC50 200.8–438.4 μg/mL) cytotoxicity level on the cancer and normal cells, respectively. While relatively lower serum testosterone levels and total sperm count along with decreased numbers of spermatogonia were noted in the untreated group, all these parameters were improved in the groups treated with the extracts at 250 mg/kg. Improved histomorphological changes of the testes were also observed when compared to the untreated group. While the extracts (at 250 mg/kg) increased serum reduced glutathione content and decreased malondialdehyde content, a relatively higher serum creatinine level was also observed in the treated animals group. The results indicate that the two plant extracts have potential to ameliorate testicular dysfunction.


2020 ◽  
Author(s):  
Arezoo Afshari ◽  
Fouzieh Salimi ◽  
Masumeh Babaie ◽  
Salar Bakhtiyari ◽  
Gholamreza Hassanzadeh ◽  
...  

Abstract Background: The extent of metabolic disruption and the usefulness of drugs and supplements, such as medicinal plants, in patients with diabetes may be impacted by the severity of the disease. Method: Nicotinamide + STZ together and STZ alone were used to induce early- and late-stage diabetes type 2 (ET2D and LT2D, respectively) in rats. Glucose tolerance test (GTT) was performed because the stage of disease was considered compatible with the magnitude of deviation from normal glucose tolerance test (GTT), as well as the level of FBS. Three main groups of the study were nondiabetic, early-stage diabetic, and late-stage diabetic rats. Each group was divided into two sub-groups, one of which received Citrullus colocynthis seed aqueous extract (CCAE, 90mg/kg BW) for 28 days. Weekly FBS and body weights were recorded during the study. At the end of 28 days, the serum levels of ALT, AST, ALP, TG, urea, creatinine, uric acid, cholesterol, HDL, LDL, c-peptide, and HbA1c were measured; the hepatic mRNA expression of several enzymes of glucose and fat metabolic pathways were also determined by Real-Time PCR. The accumulation of fat in the hepatic tissue was visualized by measuring the TG content and by H&E and Oil-Red staining and the degree of oxidative stress was measured by protein carbonyl content (PCC).Results: The LT2D rats showed maximal deviations from normal GTT. GTT for control and ET2D rats were similar, yet the area under curve (AUC) for ET2D rats was significantly higher. Urea, ALT, and ALP levels were high in diabetic rats compared to control and significantly different from each other.Serum TG dropped and ALT, ALP, HDL and LDL significantly improved after treatment with CCAE. Different patterns of G6Pase and PEPCK expression in ET2D and LT2D suggested their similarity to short- and long-term fasting states, respectively. While the reduction of FBS levels in ET2D could be explained by an inhibition of G6Pase expression and therefore glycogenolysis, the level of PEPCK expression was not significantly lowered by CCAE in LT2D. H&E staining of liver tissue showed steatoses of varying morphology in both ET2D and LT2D rats. CCAE led to up-regulated PPARα and down-regulated CPT1 expressions.Conclusion: As PEPCK activity is necessary for the continuation of the TG/FA cycle during fasting, it is possible that in LT2D, CCAE directed the PEPCK activity more towards glyceroneogenesis than gluconeogenesis to ensure the persistence of the TG/FA cycle. The enhanced glyceroneogenesis together with an up-regulated PPARa expression and down-regulated CPT1 expression probably led to lower blood and hepatic TG. More research is needed to establish the effect of CCAE on PEPCK expression and its course of activity.


Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1142
Author(s):  
Marwa T. Hassen ◽  
Hanaa K. Mohamed ◽  
Metwally M. Montaser ◽  
Mohamed E. El-Sharnouby ◽  
Nabil Awad ◽  
...  

Cisplatin (Cis) a drug commonly used as a chemotherapeutic agent to treat various types of cancer, inducing testicular damage. The present study aimed to investigate the inhibitory potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and beetroot extract (BRE) in albino rats after testicular toxicity induced by cisplatin. Thirty adult male albino rats were grouped into: the control group, Cis group receiving a single dose of 7 mg/kg i.p. (intraperitoneal) to induce testicular toxicity, Cis plus BM-MSCs injected Cis followed by 2 × 106 of BM-MSCs; Cis plus BRE group receiving Cis followed by 300 mg/kg body weight/day of BRE, and Cis plus BM-MSCs and BRE group. In the current study, Cis reduced sperm count, serum testosterone level, and testicular activity of alkaline phosphatase (AKP), besides a marked inhibition of succinate dehydrogenase (SDH) activity. In addition, it significantly increased malondialdehyde (MDA) and along with a marked decrease in testis reduced glutathione content and total antioxidant capacity (TAC). At the same time, Cis administration resulted in a marked elevation in interleukine-6 and the iNOS and caspase-3 genes; however, it decreased the expression of steroidogenic acute regulatory protein (StAR). Combined treatment with BM-MSCs and BRE resulted in great improvement of all previous parameters. These results were also confirmed by histopathological and immunohistochemical examination. In conclusion, both MSCs and BRE were found to have potent potentials to inhibit testicular damage induced by cisplatin.


2020 ◽  
Vol 16 ◽  
Author(s):  
Anupama Sharma ◽  
Renu Bist ◽  
Hemant Pareek

Background:: Current study evaluated the protective potential of quercetin against lindane induced toxicity in mice brain. For investigation, mice were allocated into four groups; First group was control. Second group was administered with oral dose of lindane (25 mg/kg bw) for 4 consecutive days. Third group was exposed to quercetin (40 mg/kg bw) and in fourth group, quercetin was administered 1 hour prior to the exposure of lindane. Objective:: Two major objectives were decided for study. First was to create lesions in the brain by lindane and; second was to evaluate the neuroprotective potential of quercetin. Methods:: To study oxidative responses, level of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), reduced glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT), and glutathione peroxidase (GPx) were measured in brain homogenates. Three key step regulating enzymes of tricarboxylic acid (TCA) cycle viz citrate synthase (CS), pyruvate dehydrogenase (PDH) and fumarase were also assayed. Results:: Lindane treatment significantly enhanced the levels of TBARS (P<0.001),PCC (P<0.001), GPx (P<0.001), SOD (P<0.05), PDH (P<0.05) and fumarase (P<0.001) in brains of mice compared to control. Meanwhile, it alleviated GSH, CAT and CS (P<0.05) activity. Conclusion:: Pretreatment with quercetin in lindane treated group not only restored, previously altered biochemical parameters after lindane treatment and also significantly improved them too which suggests that quercetin is not only invulnerable rather neuroprotective against lindane intoxication.


2020 ◽  
Vol 70 (2) ◽  
pp. 227-237
Author(s):  
Eda Güneş

Abstract The aim of the this study was to evaluate the effects of fresh, dried and freeze-dried Centaurea depressa M. Bieb. (Asteraceae) on the oxidant and antioxidant status of the model organism D. melanogaster Meigen (Diptera: Drosophilidae) experimentally. The study was carried out from 2016 to 2019, and plant leaf extracts (0-50 mg/l) were added to insect standard artificial diets. The total protein, protein carbonyl content and glutathione-S-transferase, superoxide dismutase and catalase activities were quantified at the insect’s third larval stage. Our data showed that protein carbonyl content varied from 2.70 nmol/mg protein in the control group to 59.11 nmol/mg protein in the group fed with fresh leaf extract signifying induction of oxidative stress. All extracts increased the levels of all antioxidant enzymes and decreased the amounts of total protein. Meanwhile, the group fed with the freeze-dried extract showed no significant difference in the levels of total protein and protein carbonyl content except at the 50 mg/l concentration of the extract. Moreover, this group had superoxide dismutase and catalase activities 4 to 5 times higher than in the control group. In conclusion, induction of oxidative stress indicates that the fresh form of C. depressa leaves may have potential as a natural pesticide, whereas induction of endogenous antioxidant enzymes by the freeze-dried extract suggest its potential as an antioxidant.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Alireza Hosseini ◽  
Mehrdad Shahrani ◽  
Shirin Asgharian ◽  
Maryam Anjomshoa ◽  
Ayoob Rostamzadeh ◽  
...  

Abstract Background Cyclophosphamide (CP) is an anti-neoplastic alkylating agent that is extensively used in different chemotherapy regimens. Adverse effects on the reproductive system, especially spermatogenesis, are one of the most important side effects of this drug. It is medically essential to use complementary and alternative drugs. Herbal drugs have long been used as a complementary treatment. Our purpose was to study the effect of hydroalcoholic Allium atroviolaceum L. extract on spermatogenesis in CP-treated mice. Results CP affected a significant decrease in sperm count, motility, viability, and morphology. Sperm count was significantly higher in the all extract groups than in the group of control (p<0.001) and CP group (p<0.001, p<0.01). Sperm motility was significantly greater in the extract (100 and 200mg/kg) groups than in the group of control (p<0.05 and <0.001). Sperm immotility and rotational movement were significantly higher in the CP group than in the CP+extract groups (p<0.001). The sperm viability was significantly greater in the CP+extract (200mg/kg) group than in the CP group (p<0.001). The number of headless sperm, sperm with initial tail, with coiled tail, and sperm with curved body, was significantly lower in the CP+extract (200mg/kg) group than in the CP group (p<0.001). Conclusion A. atroviolaceum extract treatment significantly improved CP-induced reproductive toxicity.


1991 ◽  
Vol 11 (6) ◽  
pp. 537-544 ◽  
Author(s):  
Adriana G. Prat ◽  
Caroline Bolter ◽  
Ulises Chavez ◽  
Charles Taylor ◽  
William Chefurka ◽  
...  

Author(s):  
Amal J. Fatani ◽  
Salim S. Al-Rejaie ◽  
Hatem M. Abuohashish ◽  
Abdullah Al-Assaf ◽  
Mihir Y. Parmar ◽  
...  

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
M. M. Hasan ◽  
V. Sood ◽  
C. Erkinbaev ◽  
J. Paliwal ◽  
S. Suman ◽  
...  

ObjectivesTo compare lipid (malondialdehyde [MDA], 4-hydroxy-2-nonenal [HNE]) and protein (carbonyl content [CAR]) oxidation products and determine their influence on color stability in two bison muscles (longissimus lumborum [LL; color stable] and psoas major [PM; color labile]).Materials and MethodsA total of 10 longissimus lumborun (LL) and 10 psoas major (PM) from five A1 grade bison carcasses were obtained from a commercial slaughter plant within 48 h post-mortem. From each muscle, a 10-cm thick piece was removed and subsampled for evaluation of pH, MDA (by thiobarbituric acid assay), HNE (by ELISA) and CAR (by 2,4-dinitrophenylhydrazine). These measurements allowed the establishment of a baseline for the different oxidation products. The remainder of the muscles were cut into two equal portions, and each portion was vacuum-packaged and assigned to an ageing period of 7 and 14 d at 2°C. At the end of each ageing period, each muscle portion was removed from their packages, pH measured, and steaks obtained for sensory (muscle and discoloration scores) and instrumental color measurements (L*, a* and b*) over 5 d of retail display, and for estimation of MDA, HNE and CAR. After 5 d in retail display and following color and pH measurements the steaks were removed and collected for MDA, HNE and CAR determination. Data were analyzed as a completely randomized design with a split-split plot arrangement. Additionally, correlation and regression analysis were performed to identify the influence of the measured attributes on color.ResultsRegardless of the ageing time, LL showed greater redness and lower surface discoloration by instrumental (a* value; P = 0.04) and sensory (P < 0.01) color evaluation than PM at the end of the retail display. Furthermore, LL exhibited lower MDA, HNE and CAR content compared to PM (P < 0.05). A three-way interaction (muscle × ageing time × retail day display) was detected on MDA content, where PM presented a higher level of MDA with increasing ageing time and retail display than LL (P = 0.02). The pH was not different between LL and PM (P > 0.05) steaks.In both muscles, Pearson (r) and Spearman (rs) correlation coefficients indicated that MDA was the oxidation compound showing the highest correlation to a* (r = –0.78; P < 0.01) and discoloration (rs = 0.81; P < 0.01) scores, followed by a moderate correlation with HNE and CAR (r or rs < 0.7; P < 0.01). The pH did not exhibit correlation with color traits, except for lightness, in both muscles. For the stepwise regression analysis, the main variable entered into the equation for predicting a*, color and discoloration score in PM muscle was MDA with an R2 of 0.72, 0.75 and 0.78, respectively, while for LL muscle, MDA presented an R2 of 0.62, 0.68 and 0.66;, respectively. The pH, HNE and CAR only explained an additional 2% of the variation in those attributes.ConclusionThe results of color attributes corroborated that bison LL is a color-stable muscle due to the lower level of protein and lipid oxidation products developed during storage and retail display compared to PM muscle, which is considered color-labile muscle. The MDA seemed to have remarkable importance in the color deterioration than HNE and CAR, particularly in bison PM muscle.


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