Putri Ayu Jayusman

Fenitrothion induced oxidative stress and morphological alterations of sperm and testes in male sprague-dawley rats

OBJECTIVE: Fenitrothion residue is found primarily in soil, water and food products and can lead to a variety of toxic effects on the immune, hepatobiliary and hematological systems. However, the effects of fenitrothion on the male reproductive system remain unclear. This study aimed to evaluate the effects of fenitrothion on the sperm and testes of male Sprague-Dawley rats. METHODS: A 20 mg/kg dose of fenitrothion was administered orally by gavages for 28 consecutive days. Blood sample was obtained by cardiac puncture and dissection of the testes and cauda epididymis was performed to obtain sperm. The effects of fenitrothion on the body and organ weight, biochemical and oxidative stress, sperm characteristics, histology and ultrastructural changes in the testes were evaluated. RESULTS: Fenitrothion significantly decreased the body weight gain and weight of the epididymis compared with the control group. Fenitrothion also decreased plasma cholinesterase activity compared with the control group. Fenitrothion altered the sperm characteristics, such as sperm concentration, sperm viability and normal sperm morphology, compared with the control group. Oxidative stress markers, such as malondialdehyde, protein carbonyl, total glutathione and glutathione S-transferase, were significantly increased and superoxide dismutase activity was significantly decreased in the fenitrothion-treated group compared with the control group. The histopathological and ultrastructural examination of the testes of the fenitrothion-treated group revealed alterations corresponding with the biochemical changes compared with the control group. CONCLUSION: A 20 mg/kg dose of fenitrothion caused deleterious effects on the sperm and testes of Sprague-Dawley rats.

Antioxidant activity of tocotrienol rich fraction prevents fenitrothion-induced renal damage in rats

Fenitrothion (FNT) is an organophosphate compound widely used as pesticide in Malaysia. The present study aims to investigate effects of palm oil tocotrienol rich fraction (TRF) on the renal damage of FNT-treated rats. A total of 40 male Sprague Dawley rats were divided into 4 groups randomly, the control, TRF, FNT and FNT+TRF groups. FNT (20 mg/kg b.w.) and TRF (200 mg/kg b.w.) were given orally for 28 days continuously. Rats from the FNT+TRF group were supplemented with TRF 30 minutes prior to administration of FNT. Rats were sacrificed after 28 days, and the kidneys were removed for determination of oxidative stress and histological analysis. Plasma was collected for determination of blood creatinine and urea level. Statistical analysis showed that palm oil TRF has a protective effect against renal oxidative damage induced by FNT. In the FNT+TRF group, malondialdehyde and protein carbonyl levels were significantly lower, while the glutathione level as well as superoxide dismutase and catalase activities were significantly higher compared with the FNT-treated group (p<0.05). As for renal function, there was a markedly lower urea level (p<0.05) in the FNT+TRF group compared with the FNT-treated group, but there was no significant difference in creatinine level. Besides, total protein also showed no significant difference for all groups of rats (p>0.05). Histological evaluation also revealed that the FNT+TRF group had less glomerulus and renal tubule damage than the FNT-treated group. In conclusion, palm oil TRF was able to reduce oxidative stress and renal damage in FNT-treated rats.

Fenitrothion alters sperm characteristics in rats: ameliorating effects of palm oil tocotrienol-rich fraction.

Exposure to organophosphate insecticides such as fenitrothion (FNT) in agriculture and public health has been reported to affect sperm quality. Antioxidants may have a potential to reduce spermatotoxic effects induced by organophosphate. The present study was carried out to evaluate the effects of palm oil tocotrienol-rich fraction (TRF) in reducing the detrimental effects occurring in spermatozoa of FNT-treated rats. Adult male Sprague-Dawley rats were divided into four equal groups: a control group and groups of rats treated orally with palm oil TRF (200 mg/kg), FNT (20 mg/kg) and palm oil TRF (200 mg/kg) combined with FNT (20 mg/kg). The sperm characteristics, DNA damage, superoxide dismutase (SOD) activity, and levels of reduced glutathione (GSH), malondialdehyde (MDA), and protein carbonyl (PC) were evaluated. Supplementation with TRF attenuated the detrimental effects of FNT by significantly increasing the sperm counts, motility, and viability and decreased the abnormal sperm morphology. The SOD activity and GSH level were significantly increased, whereas the MDA and PC levels were significantly decreased in the TRF+FNT group compared with the rats receiving FNT alone. TRF significantly decreased the DNA damage in the sperm of FNT-treated rats. A significant correlation between abnormal sperm morphology and DNA damage was found in all groups. TRF showed the potential to reduce the detrimental effects occurring in spermatozoa of FNT-treated rats.

The use of selective estrogen receptor modulators on bone health in men

Abstract Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men. Therefore, this evidence-based review aims to assess the available evidence derived from animal and human studies on the effects of SERMs on the male skeletal system. The effects of SERMs on bone mineral density (BMD)/content (BMC), bone histomorphometry, bone turnover, bone strength and fracture risk have been summarized in this review.

Palm oil tocotrienol-rich fraction attenuates testicular toxicity induced by fenitrothion via an oxidative stress mechanism

Palm oil tocotrienol-rich fraction (TRF) is a well known antioxidant that has shown potential in reducing oxidative stress under various pathological conditions. Exposure to organophosphates such as fenitrothion (FNT) has been reported to cause testicular oxidative damage. The present study was conducted to determine whether TRF could prevent this testicular damage. Parameters evaluated included the oxidative stress status, heat shock protein-70 (HSP70) expression, germ cell apoptosis, reproductive biochemical levels, and morphological alteration. Mature male Sprague-Dawley rats (n = 40) were given FNT (20 mg kg−1), TRF (200 mg kg−1) and TRF + FNT daily via gavage for 28 consecutive days. Co-administration of TRF in FNT-treated rats increased the activities of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione s-transferase (p < 0.05). TRF also increased the ferric reducing antioxidant power (FRAP) as well as the levels of non-enzymatic antioxidants such as glutathione, compared with the FNT group alone (p < 0.05). Further, TRF reduced lipid peroxidation and protein oxidation by significantly lowering the malondialdehyde and protein carbonyl levels in FNT-treated rats (p < 0.01). HSP70 expression and apoptotic germ cell count in the testis were significantly reduced in the TRF + FNT group (p < 0.05). TRF also ameliorated the biochemical changes in rat testis by reducing sialic acid, total cholesterol, and total protein at p < 0.05. Histological and ultrastructural observations revealed that supplementation with TRF improved the morphological changes in testis in the TRF + FNT group. In conclusion, TRF was able to partially mitigate testicular damage in FNT-intoxicated rats.

The Effects of Chemical Castration with Degarelix on Bone Turnover: Densitometric and Biomechanics Bone Properties of Male Rats

Background Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone. Objectives The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats. Methods Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis. Results Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups. Conclusions In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

The Effects of Quassinoid-Rich Eurycoma longifolia Extract on Bone Turnover and Histomorphometry Indices in the Androgen-Deficient Osteoporosis Rat Model

Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague–Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.