Protective effects of diosmin on doxorubicin-induced testicular toxicity in rat.

Doxorubicin (DOX) can be applied to treat several cancers. DOX-induced oxidative stress causes testicular damage. Diosmin (DIO), as a potent antioxidant, reduces many drugs' side effects. We determined DIO therapeutic effects on DOX-related testicular toxicity. Forty rats were assigned to five groups as control, DOX (2.5 mg/kg six i.p. injections at equal intervals over two weeks), DOX + DIO (25, 50, 100 mg/kg, orally, daily, for two weeks) groups. Oxidative and antioxidant markers, fertility parameters levels, sperm parameters, and a histopathological examination were analyzed. DOX group showed a significant decrease in the number of spermatogonia, primary spermatocytes, and sertoli cells, seminiferous tubular diameter, seminiferous luminal diameter, and seminiferous epithelial height. Moreover, testosterone levels, glutathione (GSH) levels, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities showed a significant decrease. Furthermore, nitric oxide (NO) and malondialdehyde (MDA) contents and also follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed a significant increase in the DOX group compared to the control group. DIO improved DOX-related alterations in levels of hormones, spermatogonia, spermatocytes, and sertoli cell number, and seminiferous diameters (tubular, luminal, and epithelial height). Furthermore, GSH level, SOD, GPx, and CAT activities showed a significant increase, and MDA and NO contents showed a significant decrease in the DOX + DIO group than the DOX group. The results indicate that DIO mitigate DOX-induced testicular toxicity by its anti-oxidant activity.

Gentisic acid mitigates gentamicin-induced nephrotoxicity in rats.

The current investigation was considered to evaluate the beneficial effects of gentisic acid (GA) on gentamicin (GEN)-induced nephrotoxicity in rat kidneys through assessment of oxidative stress, inflammatory cytokines, and histopathological changes. Rats were split into five equal groups. Rats were treated with GA (25, 50, and 100 mg/kg/day, p.o.) for 14 consecutive days and GEN (100 mg/kg, i.p.) was administrated from day 8 to day 14 of the experiment. On the 15th day, blood samples were collected to determine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine (Cr) levels. Malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß), and nitric oxide (NO) levels and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were assessed in the renal tissue. Histopathological evaluations were done to confirm the biochemical results. GEN increased the levels of NGAL, KIM-1, BUN, and Cr in serum as well as MDA, NO, GSH, TNF-α, and IL-1ß in renal tissue. Moreover, GEN administration reduced the activity of CAT, SOD, and GPx in renal tissue. Nonetheless, the administration of GA before and alongside GEN mitigated these deleterious effects. In conclusion, GA has a beneficial effect on biochemical, inflammatory, and oxidative stress indices against GEN-induced nephrotoxicity.

The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-ß1 signaling in rat.

Exposure to dust storm particulate matter (PM) is detrimental to kidney tissue. In this study, the impacts of chronic intake of dusty PM were explored as a major objective in a specified compartment to make a real-like dust storm (DS) model, and the role of hesperidin (HSP) as an antioxidant on kidney tissue was assessed in rats. Thirty-two male Wistar rats (200-220 g) were randomly allocated into 4 groups: CA+NS: (clean air and normal saline as a vehicle of HSP). Dusty PM and NS (DS+NS). HSP+ CA: rats received 200 mg/kg of HSP by gavage for 28 days, once daily in addition to exposure to clean air. HSP+DS: HSP plus DS. In DS groups, the animals were exposed to dust storms at a concentration of 5000-8000 µg/m3 in the chamber for 1 h daily, for 4 consecutive weeks, except Thursdays and Fridays. At the end of the experiment, the animals were sacrificed for biochemical, inflammatory, oxidative stress, molecular parameters, and histological evaluation. DS significantly enhanced blood urea nitrogen and creatinine, inflammatory (tumor necrosis factor-α, and interleukin-1ß), and oxidative stress indexes. Likewise, a significant increase was seen in mRNA Smads, collagen-I, and transforming growth factor-ß1 (TGF-ß1) expressions in the kidney. Histological findings showed contracted glomeruli and kidney structure disorder. In addition, Masson's trichrome staining demonstrated renal fibrosis. Nevertheless, HSP could significantly reverse these changes. Our data confirmed that DS results in kidney fibrosis through enhancing Smads/TGF-ß1 signaling. However, HSP was able to inhibit these changes as confirmed by histological findings.

Curcumin attenuates memory impairments and long-term potentiation deficits by damping hippocampal inflammatory cytokines in lipopolysaccharide-challenged rats.

Neuroinflammation is a key pathological event triggering neurodegenerative process, resulting in neurologic sequelae. Curcumin (cur) has recently received increasing attention due to its anti-inflammatory properties. Therefore, we investigated the protective effects of curcumin on lipopolysaccharide (LPS)-induced memory impairments, long-term potentiation (LTP) deficits, hippocampal inflammatory cytokines, and neuronal loss in male rats. Rats were randomly divided into four groups as follows: (1) Vehicle; (2) cur; (3) LPS; and (4) cur/LPS. Following curcumin pretreatment (50 mg/kg, per oral via gavage, 14 consecutive days), animals received a single dose of LPS (1 mg/kg, intraperitoneally) or saline. Twenty-four hours after LPS/or saline administration, passive avoidance test (PAT), hippocampal LTP, inflammatory cytokines (TNFα, IL-1ß), and neuronal loss were assessed in hippocampal tissue of rats. Our results indicated that pretreatment with curcumin in LPS-challenged rats attenuates memory impairment in PAT, which was accompanied by significant increase in the field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude. Hence, pretreatment with curcumin in LPS-treated rats decreased hippocampal concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß), as well as reduced neuronal loss in the hippocampal tissue. This study provide evidence that pretreatment with curcumin attenuates LPS-induced memory impairment and LTP deficiency, which may be partly related to the amelioration of inflammatory cytokines and neuronal loss in the hippocampal tissue.

Curcumin Ameliorates Neurobehavioral Deficits in Ambient Dusty Particulate Matter-Exposure Rats: The Role of Oxidative Stress.

It has been consistently found that exposure to ambient air pollution, such as particulate matter (PM), results in cognitive impairments and mental disorders. This study aimed to investigate the possible neuroprotective effects of curcumin, a polyphenol compound, on the neurobehavioral deficits and to identify the role of oxidative stress in dusty PM exposure rats. Rats received curcumin (50 mg/kg, daily, gavage, 2 weeks) 30 min before placing animals in a clean air chamber (≤ 150 µg/m3, 60 min daily, 2 weeks) or ambient dusty PM chamber (2000-8000 µg/m3, 60 min daily, 2 weeks). Subsequently, the cognitive and non-cognitive functions of the animals were evaluated using standard behavioral tests. Moreover, blood-brain barrier (BBB) permeability, brain water content (BWC), oxidative-antioxidative status, and histological changes were determined in the cerebral cortex and hippocampal areas of the rats. Our results showed that curcumin administration in dusty PM exposure rats attenuates memory impairment, decreases anxiety-/depression-like behaviors, and improves locomotor/exploratory activities. These findings were accompanied by reduced BBB permeability and BWC, decreasing oxidative stress, and lessening neuronal loss in the cerebral cortex and different hippocampal areas. The results of this study suggest that curcumin's antioxidant properties may contribute to its efficacy in improving neurobehavioral deficits and preventing neuronal loss associated with dusty PM exposure.

Determination of the Effectiveness of Topical Product of Commiphora Mukul Oleo Gum Resin on Dermal Wound Healing: An Experimental Study.

In Persian Medicine, many plants have been used in wound healing for thousands of years, and recent evidence indicates the beneficial effects of plant extracts on healing skin wounds. Commiphora mukul oleo gum resin has been considered for a long time due to its various properties such as milk-enhancing, diuretic, and healing the mouth and larynx wounds. The present study aimed to evaluate the effect of Commiphora mukul oleo gum resin on wound healing in rats. Forty-two albino Wistar rats have randomly divided into six groups: The first group was without treatment, the second group was treated with Eucerin, the third group was treated with phenytoin cream %1, the fourth to sixth groups were treated with Commiphora mukul ointment 2%, 4%, and 8% respectively. Treatment was performed once a day for 14 days, and the wound area was measured daily. At the end of the experiment, blood samples were taken to measure vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The histological evaluation and the strength test of the repaired tissue were performed. The results showed that seven days after treatment, the wound area decreased significantly in the groups treated with mukul gum extract compared to the control groups (p0.05). At the end of the experiment, there was no significant difference in wound area reduction between the groups. Commiphora mukul gum extract increased VEGF and significantly improved skin elasticity. The results of this study indicate the Wound healing potential of Commiphora mukul.

Potential protective effect of quercetin on the male reproductive system against exposure of Wistar rats to crude oil vapor: Genetic, biochemical, and histopathological evidence.

Toxic compounds in crude oil vapor (COV), including polycyclic aromatic hydrocarbons (PAHs), are associated with adverse effects on reproduction in living organisms. Quercetin (QT) is the most plentiful flavonoid in vegetables and fruits, with antioxidant activities. This study aimed to evaluate the protective role of QT on testicular toxicity induced by COV. Twenty-four adult male Wistar rats were randomly divided into four groups (n = 6) including control, quercetin (QT) (50 mg/kg), crude oil vapors (COV), and COV + QT. The inhalation method was used to expose the rats to crude oil vapors for 5 h daily, and QT was administered orally. After 30 days, the rats were euthanized, then, the testes were removed for gonadosomatic index (GSI), sperm parameters, H&E staining, the activity of the antioxidant enzymes, and apoptotic gene expression assessments. The COV statistically significantly (P < 0.05) reduced GSI, sperm count, motility, viability, and sperm normal morphology, histological indexes, and antioxidant enzyme activities than control. Also, COV statistically significantly (P < 0.05) increased the expression of caspase-3, p-53, and Bax genes and decreased Bcl-2 gene expression. Co-administration of QT + COV caused a statistically significant (P < 0.05) decrease in Bax gene expression and increased antioxidant enzyme activities, Bcl-2 gene expression, and reproductive parameters than the COV group. Based on the results of this study, it appears that crude oil vapor causes side effects on male reproduction. Yet, quercetin has the potential to reduce the side effects of crude oil vapor on the male reproductive system.

Neuroprotective effects of tannic acid against kainic acid-induced seizures in mice.

BACKGROUND: Epileptic seizures are associated with the release of potentially neurotoxic amount of glutamate, which results in the over-production of free radicals and inflammatory factors, and induction of neuronal cell death. Current study evaluated the effect of tannic acid (TA) on Kainic acid (KA)-induced seizures in mice. METHODS: Mice were divided into the six groups. Group I was administrated with normal saline (NS; 1 mL/kg, intraperitoneally (i.p.)), Group II was injected with KA (15 mg/kg, i.p.), Groups III was treated with diazepam (DZ; 20 mg/kg, i.p.) and KA (15 mg/kg, i.p.), Groups IV-VI were treated with TA (25, 50 and 100 mg/kg, i.p.) and KA (15 mg/kg, i.p.). Animals received all treatments 30 min before injection of KA. After the injection of KA, mice were observed for seizure (latency, activity and duration) and mortality for 2 h. In the brain tissue, oxidative stress, apoptosis, and inflammatory markers were evaluated in addition to the determination of histological alterations in the CA1 molecular layer of hippocampus. RESULTS: Treatment with TA significantly increased seizure latency and decreased seizure duration and activity, but could not significantly decrease mice mortality. This effect was associated with the reduction of oxidative stress, inflammation, and apoptosis. Furthermore, treatment with TA significantly improved KA-induced pyramidal cell loss and change in the arrangement of CA1 molecular layer. CONCLUSIONS: Tannic acid may be useful in the control of epileptic seizures through regulating oxidative stress, inflammation and apoptosis.

Gallic acid ameliorates di-(2-ethylhexyl) phthalate-induced testicular injury in adult mice.

Background: Di-(2-ethylhexyl) phthalate (DEHP) is a well-known endocrine-disrupting compound inducing degeneration of testes. Gallic acid (GA) is a polyphenol with various pharmacological properties, including antioxidant and anti-inflammatory effects.Purpose: This research evaluated effects of different doses of GA on DEHP-induced testicular injury in adult mice.Research Design: Male mice were randomly divided into five groups and treated with agents for two weeks; group (I) received normal saline and corn oil (5 mL/kg/day, p. o.), group (II) received DEHP (2 g/kg/day, dissolved in corn oil, p. o.), groups (III, IV, and V) received DEHP + GA (25, 50, and 100 mg/kg/day, p. o.). Body and testes weights, serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were evaluated. The number of sperms and sperm motility and viability were analyzed in the cauda epididymis. Histological changes, oxidative/nitrosative stress markers, and inflammatory cytokines levels were examined in testes.Results: Body and testes weights, the number of spermatogonia, primary spermatocyte and early spermatid, and late spermatid and sperm vitality, and progressive motility were significantly reduced in mice exposed to DEHP. Serum testosterone level decreased and serum LH and FSH levels increased in DEHP-exposed mice. These alterations were associated with the increased oxidative stress level and inflammatory responses in testicular tissue. Treatment with GA (50 and 100 mg/kg/day) attenuated DEHP-induced alterations in oxidative stress markers and inflammatory cytokines and reversed abnormality in sperm characteristic and number, tissue structure, and serum hormones levels.Conclusions: Results indicated that GA might be a promising agent against male gonadal toxicity induced by endocrine disrupting chemicals including DEHP.

Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats.

AIMS: Bleomycin, an important toxic anti-cancer agent, induces pulmonary fibrosis. The significance of oxidative stress and inflammation in promoting of bleomycin-induced idiopathic pulmonary fibrosis (IPF) has been reported. Thus, we evaluated the protective effects of carnosol as a robust natural antioxidant and anti-inflammatory agent for bleomycin-related IPF in rats. MAIN METHODS: Male Wistar rats (n = 40) were randomly assigned to five groups. Group 1 was administrated with saline (intratracheally) on day 7 and oral gavage of dimethyl sulfoxide (DMSO, 0.05%) from day 1 to day 28. Group 2 received a single dose of bleomycin (intratracheally, 7.5 UI/kg) on day 7 and oral gavage of saline for 28 days. Groups 3, 4 and 5 were administrated with bleomycin (single dose) on day 7, along with oral administration of carnosol (at doses 10, 20 and 40 mg/kg, respectively) from day 1 to day 28. The lungs were isolated to measure the histopathological and biochemical and inflammatory markers. KEY FINDINGS: Carnosol treatment significantly reduced malondialdehyde, nitric oxide, protein carbonyl, tumor necrosis factor- α, interleukin-6 levels and myeloperoxidase activity in the lungs of rats exposed to bleomycin. Also, lung glutathione content, catalase, glutathione peroxidase and superoxide dismutase activities significantly increased in the carnosol/bleomycin-treated group than the bleomycin group. Lung index, hydroxyproline content, fibrosis and histopathological changes, also significantly decreased by carnosol therapy. SIGNIFICANCE: Treatment with carnosol can modulate biochemical and histological alterations caused by bleomycin. Thus, it can be regarded as an appropriate therapeutic approach for IPF.

Chrysin attenuates sodium arsenite-induced nephrotoxicity in rats by suppressing oxidative stress and inflammation.

BACKGROUND: We aimed to study the beneficial property of chrysin (CHR) by targeting its antioxidant and anti-inflammatory effects on nephrotoxicity induced by sodium arsenite (SA). MATERIALS & METHODS: We have used the 35 male Wistar rats in five equal groups (n = 7). Normal saline in (5 ml/kg; p.o.; 21 days) was given to the control group. Sodium arsenite (10 mg/kg; p.o.; 14 days) was given to the SA group. CHR (25, 50 and 100 mg/kg; p.o.; 21 days) and SA (10 mg/kg; p.o.; 14 days from the 7th day of the experiment) was given to the SA + CHR 25, 50 and 100 groups. On the 22nd day of the experiment, the animals' bloods and kidneys were taken, and then we have performed functional, biochemical and histological assessment. RESULTS: CHR pre- and alongside administration (more potently at dose of 100 mg/kg) with SA reduced the SA-induced alterations in serum creatinine and blood urine nitrogen levels. Increased levels of protein carbonyl, myeloperoxidase, malondialdehyde and nitric oxide in kidney tissue were decreased by CHR treatment. CHR administration increased the levels of glutathione and activities of glutathione peroxidase, catalase and superoxide dismutase in renal tissue. Moreover, treatment with CHR reduced the levels of inflammatory mediators including interleukin 1 beta and tumor necrosis factor alpha in renal tissue. The renal histological lesions induced SA were mitigated by CHR treatment in dose dependent manner. CONCLUSION: The results of present study suggested that administration of CHR before and alongside with SA attenuated the renal toxic effects of SA via antioxidative stress and anti-inflammatory effects.

Mechanisms involved in the possible protective effect of chrysin against sodium arsenite-induced liver toxicity in rats.

Arsenic as a one of the most important toxic metals could induce hepatotoxicity. Previous reports revealed the significance of oxidative stress in promoting of arsenic-induced liver toxicity. The aim of the present investigation is to evaluate the effect of chrysin (CHR), a natural flavonoid with potent antioxidant activity, against sodium arsenite (SA)-induced hepatotoxicity. Thirty male Wistar rats were divided into four groups: Group 1: received normal saline (2 ml/kg/day, orally for 21 days), Group 2: received SA (10 mg/kg/day, orally for 14 days), Group 3, 4 and 5: received CHR (25, 50 and 100 mg/kg/day, respectively, orally for 21 days) and SA (10 mg/kg/day, orally for 14 days) from the 7th day. Serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were evaluated. Moreover, liver glutathione peroxidase and myeloperoxidase activity as well as levels of protein carbonylation, malondialdehyde, glutathione, catalase, nitric oxide, superoxide dismutase, tumor necrosis factor-α and interleukin-1ß were evaluated. Moreover, histological evaluation was done. Our results revealed that treatment with CHR (more potentially at the dose of 100 mg/kg/day) before and alongside with SA significantly mitigated the SA-induced hepatotoxicity. Also, the hepatoprotective effect of CHR was verified by the histological evaluation of the liver. The results of current study demonstrated that CHR (100 mg/kg/day) could mitigate the oxidative stress and inflammation induced by SA in liver tissue.