Protective Effects of Daucus carota and Piper nigrum Extracts against Methotrexate-Induced Testicular Damage in Rats.

Purpose: Doxorubicin (DOX) is a wide-spectrum antibiotic used for chemotherapy. Its side effects limit treatment. Crocin is one of the carotenoids that has both anti-inflammatory and antioxidant activities. We aimed to evaluate the effects of crocin against doxorubicin-induced testicular damage in rats. Materials and Methods: Forty Wistar rats were divided into four groups. Group 1: Control, Group 2: Crocin, Group 3: DOX, Group 4: DOX+Crocin (n=10, for all). Testis tissues were stained with Hematoxylin-Eosin. The diameters of seminiferous tubules were measured and the testicular mean histopathologic damage score (MHDS) was calculated. Vimentin expression in Sertoli cells was calculated as H-Score. Levels of Malondialdehyde (MDA), Glutathione (GSH), Catalase (CAT), and Superoxide dismutase (SOD) activities were determined in testis tissues. Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) were also calculated. Results: Atrophic seminiferous tubules were seen in the DOX group. Edema, vacuolization, and disorganization were present in the injured tubules. The MHDSs for the DOX group and control groups were 4.60±0.45 and 0.20±0.13, respectively. Both of these groups showed a significant difference. The histopathologic score was reduced after using crocin. Tubule damage considerably decreased while immunoexpression levels of vimentin and seminiferous tubule width significantly increased in the DOX+Crocin group compared to the DOX group. MDA and TOS levels were significantly increased after DOX treatment, and GSH, SOD, CAT, and TAS levels were significantly decreased. All biochemical indicators were greatly improved after receiving crocin. Conclusion: Crocin supplementation exhibited adequate beneficial effects against the testicular damage of DOX-induced function by balancing the oxidant/antioxidant status.

Protective effect of pyrrolidine dithiocarbamate against methotrexate-induced testicular damage.

We investigated the histopathological effects of methotrexate (MTX), a chemotherapeutic agent, and beta glucan (BG), an antioxidant, on rat testis. We used four groups of Sprague-Dawley male rats: MTX, MTX + BG, BG, and control. The MTX group was exposed to a single dose of MTX on the first day of experiment. The MTX + BG group was exposed to a single dose of MTX and BG on the first day of experiment followed by BG for 4 additional days. The BG group was exposed to BG for 5 days. The control group was given saline for 5 days. On day five, all animals were sacrificed and testicular tissue was evaluated for histopathology and the terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick-end labeling assay (TUNEL) was used to detect apoptosis. The apoptotic index (AI) and testicular damage increased in the MTX group compared to the other three groups. Histopathology was reduced in the MTX + BG group compared to the MTX group. Seminiferous tubule diameter was reduced in the MTX group compared to the BG group; we found no difference between control and BG groups. The thickness of th e germinal epithelium was reduced in the MTX group compared to the other groups. We found no difference in testicular weight among the groups. We compared body weight before and after the experiment; weights in the MTX and MTX + BG groups were significantly reduced compared to controls. In the control groups, we found a statistically significant increase in body weight, whereas there was no change in the BG group. We found that MTX causes deleterious effects on testicular tissue and that beta glucan may be protective.

Objectives: Methotrexate (MTX) is commonly used in the management of several malignancies and autoimmune disorders; however, testicular damage is one of the most detrimental effects of MTX administration. The current the protective effect of xanthine oxidase inhibitors either purine analogue; allopurinol (ALL) or non-purine analogue; febuxostat (FEB) in testicular injury induced by MTX in rats. Materials and methods: Thirty-two rats were randomly allocated to four groups; control (received vehicles), MTX (received single dose, 20 mg/kg, i.p.), MTX + ALL (received MTX plus ALL) and MTX + FEB (received MTX plus ALL). ALL and FEB were administered orally at 100- and 10 mg/kg, respectively for 15 days. Total and free testosterone were measured in serum. In addition, total antioxidant capacity (TAC), epidermal growth factor (EGF), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), extracellular signal-regulating kinase1/2 (ERK1/2), and total nitrite/nitrate (NOx) end products were measured in testicular tissues. At the same time, immunoexpression of HO-1in testicular tissue was measured. Histopathological examination was done. Results: ALL and FEB increased total and free serum testosterone. Both drugs showed a significant reduction in testicular MDA, NOx, TNF-α levels with an increase in TAC, EGF, and ERK1/2 levels in testicular tissue. Furthermore, both drugs enhanced HO-1 immunoexpression in testicular tissue. All these findings were parallel to the preservation of normal testicular architecture in rats treated with ALL and FEB. Conclusion: All and FEB were equally protective against testicular damage induced by MTX through anti-inflammatory, anti-apoptotic, and antioxidant actions. Their effects might be through activation of the EGF/ERK1/2/HO-1 pathway.

The aim of this research was to examine the potential ameliorative effects of chrysin (CHR) against mercuric chloride (HgCl2)-induced testicular damage in rats. For this purpose, rats were divided into four groups: Control, CHR, HgCl2 and HgCl2 + CHR. HgCl2 was administered intraperitoneally at a dose of 1.23mg/kg, and CHR was administered orally at a dose of 50mg/kg for 7 days. Biochemical, molecular and immunohistochemical analyses were performed to determine the effect of treatment-mediated changes in the testicular tissue. Based on the results obtained in testicular tissue, administration of HgCl2 was observed to lower antioxidant markers, elevate malondialdehyde (MDA) levels, and increase inflammatory marker expression in rat testicular tissue. It also led to reduced testosterone levels. Additionally, there was a decrease in the expression of antiapoptotic B-cell lymphoma 2 (Bcl-2) an apoptosis marker while the levels of Caspase-3 and Bcl-2-associated X protein (Bax) were found to be higher. The endoplasmic reticulum stress marker protein kinase R-like ER kinase (PERK) and the autophagy marker Beclin-1 showed strong immunoreactivity. Additionally, HgCl2 + CHR treatment were found to significantly reduce oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress and autophagy processes in testicular tissue. In conclusion, HgCl2 administration to rats caused testicular tissue damage compared to the other groups, but CHR treatment alleviated this damage. Overall, this demonstrates the potential ameliorative mechanisms of CHR as a possible agent for HgCl2-induced testicular damage.

The aim of this study was to investigate the antioxidant and antiapoptotic effects of Primula vulgaris extract against methotrexate (MTX)-induced testicular damage. In this study, 4 groups were formed with 8 rats in each group. Rats in group 1 were given 0.8 mg/kg physiological serum via gavage for 7 days. The rats in group 2 were administered a single dose (30 mg/kg) of MTX intraperitoneally on the first day of the study. The rats in group 3 were administered a single dose (30 mg/kg) of MTX on the first day of the study and then 100 mg/kg of aqueous extract via gavage for 7 days starting from the first day. The rats in group 4 were given 100 mg/kg of aqueous extract via gavage for 7 days. On the 8th day, the testicles and epididymis of the rats were removed under anesthesia and their blood was collected. The removed testicles were used for histological and biochemical analyses. When group 2 was compared with group 1, it was determined that seminiferous tubule diameter, epithelial thickness, sperm count, motility, vitality, and Johnsen scoring values decreased; tubule number that immature cells sloughed into the lumen and apoptotic index (AI) increased. In group 3, it was observed that seminiferous tubule diameter, epithelial thickness, sperm count, motility, vitality, and Johnsen scoring values increased; tubule number that immature cells sloughed into the lumen and AI decreased compared to group 2. When group 2 was compared with group 1, it was found that MDA values increased, and SOD and CAT values decreased in blood plasma and testicular tissue. According to the study results, it was determined that MTX caused damage to the testicle by creating oxidative stress, while Primula vulgaris reduced this damage thanks to its antioxidant effects.

The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats

Diosgenin ameliorates testicular damage in streptozotocin-diabetic rats through attenuation of apoptosis, oxidative stress, and inflammation

Protective effect of magnesium oxide nanoparticles against experimental varicocele-induced testicular damage in rats.

ABSTRACTFenvalerate (FEN), a pyrethroid insecticide used worldwide, has been shown to produce a potentially adverse effect on male reproduction. However the mechanisms are not completely understood. Thus this study aimed to (1) determine whether cellular apoptosis was involved in FEN-induced testicular damage in rats, and (2) identify the potential mechanism involved in FEN-induced apoptosis in testes. Data demonstrated that FEN markedly decreased serum testosterone levels, increased the inner diameter of seminiferous tubules, decreased the layers of spermatogenic cells, disturbed spermatogenesis and increased the number of apoptotic cells. Further, bioinformatic analysis of gene microarray in rat testis tissue showed that FEN significantly altered the expressions of genes (Krt8, Mal, Cd24, Lcn2, Phlda1, Arg2) related to apoptotic related processes. The expression pattern of these 6 genes was upregulated in FEN-treated rat testicular tissue. qRT-PCR analysis demonstrated that Phlda1, a well-documented pro-apoptotic factor, was significantly elevated by FEN. The expression of PHLDA1 testicular protein was also elevated following FEN exposure. In conclusion, our results suggest that FEN exposure induced deleterious effects on rat testes associated with Phlda1-mediated apoptosis which may act as a molecular mechanism underlying FEN induced rat testicular damage.

The search for new substances with antibacterial activities has become an urgent necessity due to the resistance of many bacteria of medical importance to antibiotics. In an attempt to seek out new antibacterial agents from plants, E. coli, S. aureus, and Salmonella spp susceptibility to the seed extracts of Tetrapleura tetraptera and Piper nigrum were assessed. A Qualitative phytochemical screening was also done to establish the various phytochemicals found in the plants. To achieve these findings, the dried seeds of Tetrapleura tetraptera and Piper nigrum were collected in the Bamenda food market and ground. Further, the powder obtained was subjected to aqueous and alcoholic extractions separately in which the alcoholic and aqueous extracts of Tetrapleura teraptera and Piper nigrum seeds were evaluated for their antibacterial potential against E. coli, S. aureus, and Salmonella spp using agar diffusion. The obtained results indicated that S. aureus and E. coli were susceptible to the alcoholic and aqueous extract of Tetrapleura tetraptera (with a MIC of 50mg/ml; 100mg/ml) respectively, for S.aureus and (25mg/ml; 50mg/ml) for E.coli. For S. aureus, susceptibility to aqueous extract of Piper nigrum shows sensitivity (with MIC of 100mg/ml). Complete resistance was registered with the alcoholic extracts of Piper nigrum. Furthermore, the phytochemical screening results indicated the presence of resins, alkaloids, glycosides, tannins, flavonoids (present in all powder), and saponins (absent only in Piper nigrum). In conclusion, the alcoholic and aqueous extract of Tetrapleura tetraptera seeds has antibacterial activity against S. aureus and E. coli. It was proposed that further studies should be carried out on the susceptibility of Tetrapleura tetraptera to other bacteria.

ObjectiveThe present study aimed to investigate the possibility that curcumin (CMN) protects against methotrexate (MTX)-induced testicular damage by affecting the phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways.MethodsEighteen male Wistar albino rats were randomly divided into three groups. The control group was given an intragastric administration of dimethyl sulfoxide (DMSO) daily for 14 days, the MTX group was given a single intraperitoneal dose of MTX (20 mg/kg) on the 11th day, and the MTX+CMN group was given intragastric CMN (100 mg/kg/day, dissolved in DMSO) for 14 days and a single intraperitoneal dose of MTX (20 mg/kg) on the 11th day. At the end of the experiment, all animals were sacrificed and the testicular tissues were removed for morphometry, histology, and immunohistochemistry. Body and testicular weights were measured.ResultsBody weights, seminiferous tubule diameter, and germinal epithelium height significantly decreased in the MTX group compared to the control group. Whereas, the number of histologically damaged seminiferous tubules and interstitial space width significantly increased in the MTX group. In addition, the number of p-p38 MAPK immunopositive cells and the immunoreactivity of NF-κB also increased in the MTX group compared to the control group. CMN improved loss of body weight, morphometric values, and histological damage due to MTX. CMN also reduced the number of p-p38 MAPK immunopositive cells and the NF-κB immunoreactivity.ConclusionCMN may reduce MTX-induced testicular damage by suppressing the p38 MAPK and NF-κB signaling pathways.

Background: Methotrexate (MTX) can cause oxidative stress-related tissue damage.Vitamin E neutralizes lipid peroxidation arising from the effect of free oxygen radicals.In this study, the protective effect of vitamin E against possible MTX-related testicular damage was analyzed. Method: Thirty two mature male Spraque dawley rats were grouped as MTX, Vitamin E, MTX+Vitamin, Control groups. 20 mg/kg MTX intraperitoneal (i.p.) was applied to MTX Group in the first day; 100mg/kg i.p. vitamin E was applied to Vitamin E Group for 5 days; 20 mg/kg i.p. MTX in the first day and 100 mg/kg i.p. vitamin E for 5 days were applied to MTX+Vitamin E Group;2 ml physiological saline solution (i.p.) was applied to Control Group for 5 days. Histopathology, flow cytometry and apoptosis were evaluated on testicular tissue. Result: Apoptotic Index (%) and testicular damage were highest for MTX Group, and significant decrease was observed for MTX+Vitamin E Group compared to MTX Group.Seminiferous tubule size significant decreased in MTX Group and it increased in MTX+Vitamin E Group compared to MTX Group. No significant difference was found between MTX and MTX+Vitamin E Groups regarding germinal epithelium thickness and testicle weights. Conclusion: The results show that MTX can cause structural disruptions in testicles and vitamin E can rehabilitate MTX-related testicular damage.

Degradation of Extracellular DNA by DNase1 Significantly Reduces Testicular Damage After Testicular Torsion in Rats

Testicular damage is one of the most deleterious effects whenever cisplatin (CIS) is employed in cancer chemotherapy. Oxidative stress has been proven to be involved in CIS induced toxicity. Thus, the current study explored the possible protective effect of L-carnitine (L-CAR) against cisplatin-induced testicular damage in rats. L-carnitine (500 mg/kg/day; i.p.) was injected for 15 days, whereas cisplatin (10 mg/kg; i.p.) was injected as a single dose at the 12th day to induce testicular damage in adult male Sprague-Dawley rats. In the current study, CIS reduced the reproductive organs weight, sperm count, sperm motility and serum testosterone level beside a marked increase in the incidence of sperm abnormalities. In addition, it significantly increased malondialdehyde (MDA) and nitric oxide (NO) along with a marked decrease in testis reduced glutathione (GSH) content and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. At the same time, CIS administration resulted in marked elevation in tumor necrosis factor-α (TNF-α) production and nuclear factor-kabba B (NF-κB) expression. These results were confirmed by histopathological examination. Treatment with L-CAR markedly attenuated cisplatin-induced injury by suppression of oxidative/nitrosative stress and inflammation, amendment of antioxidant defenses, as well as improvement of steroidogenesis, spermatogenesis and testicular histological features. This study suggests a novel therapeutic application for L-carnitine as a protective agent against cisplatin-induced testicular toxicity through its promising anti-inflammatory and antioxidant capacities.