The protective effect of crocin on cisplatin-induced testicular impairment in rats

Cisplatin (CIS) is an antineoplastic drug able to produce free radicals that are capable to induce various side effects in different tissues. Hydrogen sulfide (H2S) has notable antioxidant, anti-apoptotic, and anti-inflammatory effects in different systems but its role in male reproductive system is not fully understood. In the present research, the effect of sodium hydrosulfide (NaHS) on cisplatin-induced testicular toxicity in male rats was studied. Thirty-two Sprague-Dawley rats were equally divided into 4 groups. The control group was treated with normal saline by intraperitoneal injection. The NaHS group received NaHS (200μg/kg/day) intraperitoneally for 15days. The CIS group received single dose of cisplatin (5mg/kg) intraperitoneally, while the combination of CIS and NaHS was given to the CIS+ NaHS group. At the end of the study, body and testicular weights, plasma testosterone level, histological and morphometrical alterations, inflammation via IL-1β protein, lipid peroxidation, and activity of antioxidant enzymes (including glutathione peroxidase, superoxide dismutase, and catalase) of testicular tissue were evaluated. CIS injection revealed a significant decrease (p < 0.01) in body and testis weights, plasma testosterone concentration, diameter of seminiferous tubules, germinal epithelium thickness, the number of Sertoli cells, spermatogonia and spermatocyte, Johnsen's testicular score, and testicular antioxidant enzymes, whereas it caused a significant increase (p < 0.01) in lumen diameter of the seminiferous tubules, level of lipid peroxidation, and IL-1β protein expression when compared with the control group. NaHS administration to CIS-treated rats provided marked improvement (p < 0.05) in all biochemical, histological, and morphometrical changes induced by CIS. The beneficial effects of NaHS were mediated, at least partly, by its antioxidant and anti-inflammatory properties.

Background The primary cause of glaucomatous optic nerve damage is apoptosis of nerve cell and disorder of retinal circulation.Erigeron breviscapus is confirmed to have a protective effect on retinal ganglion cells (RGCs) in rats with chronic ocular hypertension, and crocin has the effect of anti-inflammation and anti-apoptosis.However, whether crocin can protect RGCs against ocular hypertension damage is unclear. Objective This study was to investigate the protective effect of crocin on the optic nerve in chronic ocular hypertension. Methods Thirty-two SD rats were randomized into the sham operation group, model control group, erigeron group and crocin group, 8 rats for each group.The right eyes served as experimental eyes.Chronic ocular hypertensive models were established by episcleral vein cauterization in the rats of the model control group, erigeron group and crocin group, and only conjunctiva was cut off in the sham operation group.Erigeron (150 mg/kg) and crocin (20 mg/kg) was intraperitoneally injected in the erigeron group and crocin group respectively 30 minutes before operation and once daily after operation for 4 weeks, and 0.5 ml normal saline was used in the sham operation group and model control group.Intraocular pressure (IOP) was measured before surgery and 1 day, 3 days, 1 week, 2 weeks, 3 weeks and 4 weeks after surgery.The samples of eyeballs and optic nerve in the rats were prepared at 4 weeks after surgery.Retinal thickness was measured by hematoxylin and eosin staining.The apoptosis of RGCs was detected by TUNEL assay.The ultrastructure change of optic nerve was examined under the transmission electron microscope, and the expression of bcl-2 and bax proteins in retinal homogenates was analyzed by Western blot.The use and care of the animals followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Committee. Results The IOPs were significantly elevated in the model control group, erigeron group and crocin group in comparison with the sham operation group, and the IOPs was significantly higher in various time points after surgery than that before surgery (Fgroup=169.079, P=0.000; Ftime=50.505, P=0.000). The retinal thickness was (192.72±4.28), (165.15±3.89), (177.75±3.35) and (182.48±4.12)μm in the sham operation group, model control group, erigeron group and crocin group, and rat retinal thickness in the crocin group was significantly lower than that in the sham operation group and higher than that in model control group and erigeron group (all at P<0.05). The percentage of apoptotic RGCs in the sham operation group, model control group, erigeron group and crocin group, showed significant reduction in comparison with the model control group and erigeron group (all at P<0.05). The number of myelinated nerve fibers and bcl-2/bax values were significantly increased in the crocin group compared with the model control group and erigeron group (all at P<0.05). Conclusions Crocin affords a optic nerve by inhibiting RGC apoptosis and optic nerve degeneration in SD rats with chronic ocular hypertension, and the protecting effect of crocin is more prominent than that of erigeron breviscapus. Key words: Crocus/chemistry; Herbal medicine; Plant extracts/pharmacology; Ocular hypertension; Apoptosis; Retinal ganglion cells; Erigeron/chemistry; Optic nerve protection

Objective To investigate the protective effect of crocin on oxidative stress cell model of PC12 cell and the effect of crocin on PI3K/Akt signal pathway, as well as further explore the mechanism of protective effect on model cells. Methods Cells were divided into control group, model group, crocin group and VE group. The cell survival rate was detected by MTT method, and the expression of mRNA and protein of PI3K/Akt were detected by RT-PCR and Western blot. Results With the crocin concentration in 0.625 μM and 5 μM, the cell survival rate increased in a dose-dependent manner. The average optical density rate of PI3K and Akt mRNA were 0.435±0.044 and 0.375±0.034, and the PI3K and Akt protein were 0.378±0.038 and 0.386±0.043 of crocin group.Compared with the model group, the expression levels of PI3K/Akt increased in crocin group(P<0.05). Conclusion These results indicate that the antioxidant and antiapoptosis effects of crocin are induced via increasing expression of PI3K and pAkt. Key words: Crocin; Oxidative stress; Apoptosis; PI3K/AKT

Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

Panax ginseng (PG) is a medicinal plant used for many years to treat many diseases. The current study aimed to investigate the possible prophylactic and therapeutic effects of PG extract on doxorubicin (DOX)-induced testicular toxicity in rats. 32 adult male Sprague–Dawley rats (200–250 g) were used in the experiment. The experimental groups were designed as control (normal saline, intraperitoneal), DOX (18 mg/kg, intraperitoneal), PG (200 mg/kg, gavage), and PG + DOX (200 mg/kg, gavage). After treatment, serum levels of testosterone, interleukin-1β (IL-1β), glutathione (GSH), luteinizing hormone (LH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), catalase (CAT), follicle stimulating hormone (FSH), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) were measured. Then, gene expression, histopathological, and immunohistochemical analyses were performed on testicular tissues. Compared to DOX, treatment with PG + DOX showed a significant improvement in serum levels of FSH, testosterone, LH, TNF-α, IL-1β, MDA, SOD, LDH, GSH, and CAT. It was also observed that PG + DOX decreased nuclear factor-κB and cyclooxygenase-2 expression levels, increased androgen receptor expression, restored testicular histopathological structure, and significantly improved spermatogenesis. The results of the present study showed that PG may have an ameliorative effect against DOX-induced male reproductive toxicity, as DOX causes male reproductive toxicity. It can be concluded that PG is one of the effects that protect against DOX-induced testicular toxicity in rats by reducing lipid peroxidation and activating the antioxidant system. In light of this information, PG may be a useful agent to prevent the testicular toxicity observed in men receiving DOX treatment.

Roflumilast protects from cisplatin-induced testicular toxicity in male rats and enhances its cytotoxicity in prostate cancer cell line. Role of NF-κB-p65, cAMP/PKA and Nrf2/HO-1, NQO1 signaling

Crocin, the main active saffron constituent, mitigates dichlorvos-induced oxidative stress and apoptosis in HCT-116 cells.

In recent years, the use of the antioxidant in reducing heavy metal toxicities has increased worldwide. Curcumin has been reported to have a strong antioxidant activity. In this study, we investigated the protective effects of curcumin on lead acetate-induced testicular damage in rats. The sample used 40 male rats divided into 5 groups: negative control (rats were given daily with corn oil); positive control (rats were given daily with lead acetate 50 mg/kg BW orally once in a day for 35 days); and the treatment group (rats were given the curcumin 100 mg, 200 mg, and 400 mg/kg BW orally once in a day for 40 days, and on the 5th day, were given lead acetate 50 mg/kg BW one h after the curcumin administration). After 40 days, levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in testicular tissue, and sperm count, motility and viability in the epididymis were measured in rats. Testis samples were also collected for histopathological studies. Results showed that lead acetate administration significantly decreased the SOD, GPx, and increased MDA levels. Lead acetate also decreased the sperm count, motility, viability, and altered histopathological testis (testicular damage, necrosis of seminiferous tubules and loss of spermatid) compared to the negative control. However, administration of curcumin significantly improved the histopathological in testis, increased the sperm count, motility, viability, and also significantly increased the SOD, GPx, and decreased MDA in testis of lead acetate-treated rats. From the results of this study we concluded that the curcumin could be a potent natural product provide a promising protective effect against lead acetate induced testicular toxicity in rats.

Protective effects of crocin against gentamicin-induced damage in rat testicular tissue: Modulating the levels of NF-κB/TLR-4 and Bax/Bcl-2/caspase-3 signaling pathways.

Objective The detrimental effect of gamma radiation on testicular tissue is an intricate problem in the field of nuclear medicine. Therefore, this study aimed to investigate the potential mechanism of carvacrol against testicular toxicity induced by γ-rays based on bioinformatics and in vivo experiments. Methods The carvacrol targets were retrieved from the SwissTargetPrediction database. In addition, the targets for radiation-induced testicular damage were identified from the GeneCards database. However, the common potential targets were identified. Subsequently, GO and KEGG enrichment was conducted by using the KOBAS server. However, animals in the in vitro experiment were used to validate the in-silico analysis. In particular, the oxidative stress markers, including malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT), as well as testis and sperm characteristics and serum testosterone level were examined to unveil the crucial of carvacrol in γ-rays induced testicular damage. Results The findings explored that γ-rays induced testicular damage by markedly increasing oxidant markers, MDA, and substantially decreasing antioxidant markers, including GSH, TAS, SOD, and CAT. Additionally, radiation adversely affected testis and sperm characteristics and serum testosterone levels. However, bioinformatic analyses explored that the carvacrol target regulates the oxidation-reduction and testosterone biosynthesis processes. Additionally, experimental analysis explored that carvacrol improved the testis and sperm characteristics and oxidative stress. Conclusion The study revealed that carvacrol could reduce testicular toxicity in γ-irradiated rats via its antioxidant activity. Additionally, the study could benefit patients receiving radiotherapy.

Effect of Thaumatococcus daniellii leaf rat-feed on potassium bromate induced testicular toxicity

Background: The aim of this study was to investigate the protective effects of crocin against tissue damages and leukocyte infiltration induced by renal ischemia/reperfusion. Methods: In this experimental study, 35 male Wister rats weighing 250-300 g were randomly divided into 5 groups; 1. Operated controls, but no vessel occlusion was considered and passed during equivalent reperfusion period for Sham group. The second group received solvent of crocin and went through surgery, bilateral renal ischemia for 30 min and 24-h reperfusion period (I/R). The rest (group 3-5) underwent Ischemia/reperfusion and received a dose of crocin with 100, 200 or 400 mg/kg,ip respectively. At the end of reperfusion period, the right kidney tissue were collected and after staining with haematoxylin-eosin, subjected to microscopic study. Results: Following ischemia/reperfusion, the Bowman's space size, cell necrosis in the tubules of the cortex and outer medulla, vascular congestion and tubular casts in the outer and inner medulla increased. However, RBCs number in glomerular capillaries decreased and all these injuries were improved considerably via taking crocin using every three doses. In addition, ischemia/reperfusion leads to partially severe infiltration of lymphocytes into interstitial space (P<0.001), and crocin could decrease their infiltration significantly. Conclusion: Intraperitoneal administration of Crocin has protective effects against 30 min ischemia and 24-h reperfusion induced tissue damages as well as leukocyte infiltration in kidneys.

Ameliorative effect of desloratadine against cisplatin-induced renal and testicular toxicity in rats: Attention to TLR4/NLRP3 inflammasome signaling pathway

Prophylactic role of β-carotene against acrylonitrile-induced testicular toxicity in rats: Physiological and microscopical studies

This study examined how a methanolic extract of the macrofungal Pleurotus ostreatus protected rats' testicles from the toxicity caused by potassium cyanide (KCN). For 60 days, KCN was taken orally at a dose of 1.5 mg/kg body weight, either with or without Pleurotus ostreatus methanol extract (100, 200, and 400 mg/kg). Testicular histopathology, body and organ weight, organosomatic indices, serum testosterone, epididymal sperm count, testicular lipid peroxidation, and antioxidant enzyme activities (catalase and superoxide dismutase) were assessed. Lipid peroxidation was significantly increased by KCN intoxication, while antioxidant enzyme activities, serum testosterone levels, and the number of epididymal sperm were all significantly reduced. Additionally, testicular degenerations were noted. The co-administration of KCN and Pleurotus ostreatus extract resulted in a significant reduction in lipid peroxidation and an increase in antioxidant enzyme activities, serum testosterone concentration, epididymal sperm count, and testicular histology restoration. This finding implies that by strengthening the antioxidant defense system, Pleurotus ostreatus may be able to lessen the harmful effects of dietary cyanide toxicity on testicular function.