Chemical characterization and effect of Ziziphora clinopodioides green-synthesized silver nanoparticles on cytotoxicity, antioxidant, and antidiabetic activities in streptozotocin-induced hepatotoxicity in Wistar diabetic male rats.

The present research studied the cytotoxicity, antioxidant, and antidiabetic activities of biogenically synthesized silver nanoparticles (AgNPs) using Ziziphora clinopodioides (Z. clinopodioides) as a green mediator. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy (UV-Vis) were employed to determine AgNPs. In the in vivo experiment, the model rats were categorized into different groups receiving 50, 100, 200, and 400 µg/kg of AgNPs and diabetic, positive, and normal groups (n = 10) using a random division. A single dose of streptozotocin (STZ) at 60 mg/kg was administered to induce diabetes and hepatotoxicity in rats. The administration of AgNPs was performed via intragastric administration for 25 days. On the final day, the levels of glucose and biochemical enzymes, namely aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT), were assessed in the serum. Following tissue processing, liver sections with a thickness of 5 µm were prepared. Later, the total volume of different liver components, such as hepatocytes, sinusoids, portal vein, central vein, hepatic arteries, and bile ducts, was measured. The portal vein and bile duct volumes did not vary significantly in groups treated by AgNPs. However, the volume of the central vein and hepatic arteries exhibited noticeable variations in groups treated by AgNPs. After administration of streptozotocin, the volume of hepatocytes and sinusoids increased significantly. However, treatment with a high dose of AgNPs significantly decreased the volume of hepatocytes and sinusoids. In diabetic rats, administering AgNPs reduced the fasting blood glucose levels compared to the model group. In addition, AgNPs decreased the elevated levels of AST and ALP enzymes in a manner that depended on the dosage of AgNPs used. This research demonstrates the hepatoprotective and antidiabetic properties of AgNPs, suggesting their potential implications as hepatoprotective and antidiabetic supplements to prevent diabetes.

Risk of Pesticides Mixtures in Rice to Birds and Humans in Iran.

Rice is a staple in the diet of nearly half of the world's population. As with most crops, pesticides are used as a tool to increase crop yield in rice farming. This study investigated the residues of 14 organophosphate insecticides and 2 herbicides in rice cultivated at five locations in the southwest of Iran. The pesticide residues were then used to estimate the risk that they may pose to the health of bird and human consumers. The rice samples from the five locations contained residues from 10 to 13 pesticides. Of the 16 pesticides measured, the mean concentration of 12 pesticides exceeded the maximum residue limit set by the Iranian National Standards Organization at two or more of the sampling sites. The greatest total exceedance (sum of all pesticides detected in rice) of the species sensitivity distributions constructed for birds was 0.74% and the level of concern set for the assessment was an exceedance ≥ 5%, which suggests a relatively low risk to birds. For human consumers, no single pesticide measured in rice samples posed a considerable risk. However, when considering the mixture of pesticides present in rice samples, the cumulative risk exceeded the level of concern in all samples from all sites. The margin of safety for the mixture of pesticides present in rice samples ranged from 5.8 to 29.1, with 1 being the level of concern. The results of this study indicate that efforts need to be made to mitigate the exposure of human consumers to pesticides present in rice cultivated in Iran. This study also highlights the need to collect data on pesticides residues in other crop cultivated in Iran.

Detection of different variants of SARS-CoV-2 RNA (genome) on inanimate surfaces in high-touch public environmental surfaces.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease started in late 2019 and still continues as a global pandemic, spreading among people around the world. There is limited knowledge about the role of contaminated environmental surfaces, especially high-touch public surfaces, in the transmission of the disease. The objective of the present investigation was detection of different variants (Delta, UK, and Omicron) of SARS-CoV-2 RNA (genome) on inanimate surfaces in high-touch public environmental surfaces in different seasons. Automated teller machines of banks (ATM), point-of-sale (POS) machine, gas station pump nozzles, and escalator handrails of malls were selected as high-touch environmental surfaces in public places. Overall, 75 samples were collected from these places and examined for the presence of SARS-CoV-2 RNA (genome), and 21 samples (28%) were positive. Although the role of fomite transmission of COVID-19 is understood, more studies should be conducted to determine the virus survival rate as well as the required efforts to prevent the spread of SARS-CoV-2 such as frequent cleaning and the use of efficient disinfectants on environmental surfaces, especially high-touch public places. In conclusion, the results address the importance of touching contaminated inanimate objects as well as transmission through environmental surfaces, and they could be used to establish an effective protocol to prevent indirect environmental transmission of SARS-CoV-2, slow down the spread of the virus, and reduce the risk of infection.

Role of bio-electrochemical technology for enzyme activity stimulation in high-consumption pharmaceuticals biodegradation.

Active pharmaceutical ingredients (APIs) and their intermediate residues have recently been considered a serious concern. Among technologies, bio-electrochemical technologies (BETs) have stimulated the production of bio-electrical energy. This review aims to examine the benefit and mechanism of BETs on the degradation of high-consumption pharmaceutical compounds, including antibiotic, anti-inflammatory, and analgesic drugs, and the stimulation of enzymes induced in a bioreactor. Moreover, intermediates and the proposed pathways of pharmaceutical compound biodegradation in BETs are to be explained in this review. According to studies performed exclusively, the benefit of BETs is using bio-electroactive microbes to mineralize recalcitrant pharmaceutical contaminants by promoting enzyme activity and energy. Since BETs use the electron transfer chain between bio-anode/-cathode and pharmaceuticals, the enzyme activity is essential in the oxidation and reduction of phenolic rings of drugs and the ineffective detoxification of effluent from the treatment plant. This study is suggested a vital and influential role of BETs in mineralizing and enzyme induction in bioreactors. Eventually, a content of future developments or outlooks of BETs are propounded to improve the pharmaceutical industries' wastewater problems.

Diosmin prophylaxis reduces gentamicin-induced kidney damage in rats.

Gentamicin is an essential aminoglycoside antibiotic, but it is only used to treat severe bacterial infections due to its high nephrotoxicity in patients. We evaluated the preventive effects of diosmin (as a natural ingredient) on gentamicin-related kidney damage in rats. In this research, 28 male Wistar rats were divided into four groups: control, gentamicin (100 mg/kg (i.p.), daily for 1 week), gentamicin plus diosmin (50 mg/kg, p.o., daily for 2 weeks), and diosmin (50 mg/kg/day, p.o. for 2 weeks). After the final gavage, blood samples were collected for the determination of blood urea nitrogen (BUN) and creatinine. Kidneys are used for biochemical, inflammatory, and histological tests. The concentrations of creatinine, BUN, nitric oxide, malondialdehyde, tumor necrosis factor α (TNF-α), and interleukin 1 beta (IL-1ß) were significantly increased. But, the level of glutathione and activities of catalase, glutathione peroxidase, and superoxide dismutase decreased during treatment with gentamicin. On the other hand, the concentrations of creatinine, BUN, nitric oxide, malondialdehyde, TNF-α, and IL-1ß were significantly reduced, and the glutathione level, activities of catalase, and glutathione peroxidase were significantly increased via co-administration with diosmin. Diosmin had ameliorative impacts against gentamicin-related kidney injury due to its antioxidant and anti-inflammatory activities.

Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice.

PURPOSE: Cyclophosphamide is an alkylating agent with nephrotoxicity that constrains its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. METHODS: Forty animal subjects were randomly separated into five categories of control (Group I), cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor-α (TNF-α) and interleukin 1 beta (IL-1ß) levels as inflammatory mediators were assessed in kidney tissue. RESULTS: The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1ß and increasing the level of GSH, CAT, SOD, and GPx activities. CONCLUSION: Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice.

BACKGROUND: Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects. OBJECTIVE: The current research aimed at evaluating the GA effect on CP-related renal toxicity. METHODS: In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1ß, TNF-α levels were assessed in renal tissue. RESULTS: CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1ß, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect. CONCLUSION: Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.

Berberine ameliorates testosterone-induced benign prostate hyperplasia in rats.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a major urologic problem that mostly develops in older males. Oxidative stress and inflammation influence the occurrence of BPH. Berberine (BBR) is a natural ingredient that has antioxidant and anti-inflammatory properties. The current research aims at examining the effects of BBR on testosterone-stimulated BPH in rats. METHODS: Animals were randomly categorized to six groups. In the control group, normal saline and olive oil were injected as the vehicle. BPH group: received testosterone (3 mg/kg, subcutaneous, 28 days), BPH + BBR groups; received BBR (25 and 50 mg/kg, p.o, 28 days), BPH + finasteride groups: received finasteride (1 mg/kg, p.o, 28 days), BBR (50 mg/kg, p.o, alone) was administered for subjects in the BBR group. On the 29th day, after anesthesia, cervical dislocation was used to kill the subjects. Serum concentration of testosterone and dihydrotestosterone was measured and prostate tissues were excised and used for biochemical, inflammation, and histological analysis. RESULTS: BBR prevented increased serum concentrations of testosterone and dihydrotestosterone. BBR considerably reduced BPH-stimulated oxidative stress and inflammation through preventing the rise in lipid peroxidation and nitrite concentration and declined the accumulations of pro-inflammatory cytokines (e.g. interleukin 1ß and tumor necrosis factor α) and declining the depletion rate of GSH and the function of catalase and superoxide dismutase. Histopathological investigations reported that administration of BBR could suppress testosterone-stimulated BPH. CONCLUSION: This study demonstrated that BBR could significantly prevent the development of BPH in rats.

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.

The SARS-CoV-2 (COVID-19) pandemic in hospital: An insight into environmental surfaces contamination, disinfectants' efficiency, and estimation of plastic waste production.

The current COVID-19 pandemic that is caused by SARS-CoV-2 has led all the people around the globe to implement preventive measures such as environmental cleaning using alcohol-based materials, and social distancing in order to prevent and minimize viral transmission via fomites. The role of environmental surface contamination in viral transmission in within hospital wards is still debatable, especially considering the spread of new variants of the virus in the world. The present comprehensive study aims to investigate environmental surface contamination in different wards of a hospital as well as the efficacy of two common disinfectants for virus inactivation, and tries to produce an estimate of plastic residue pollution as an environmental side effect of the pandemic. With regard to environmental surface contamination, 76 samples were taken from different wards of the hospital, from which 40 were positive. These samples were taken from contaminated environmental surfaces such as patient bed handles, the nursing station, toilet door handles, cell phones, patient toilet sinks, toilet bowls, and patient's pillows, which are regularly-touched surfaces and can pose a high risk for transmission of the virus. The number of positive samples also reveals that SARS-CoV-2 can survive on inanimate surfaces after disinfection by ethanol 70 % and sodium hypochlorite (0.001 %). The results correspond to the time that the VOC 202012/01 (lineage B.1.1.7) had emerged in the hospital and this should be considered that this variant could possibly have different traits, characteristics, and level of persistence in the environment. The plastic waste as an environmental side effect of the pandemic was also investigated and it was confirmed that the amount of plastic residue for a single (RT) PCR confirmatory test for COVID-19 diagnosis is 821.778 g of plastic residue/test. As a result, it is recommended that for improving plastic waste management programs, considering challenges such as minimizing plastic waste pollution, optimization of gas control technologies in incinerators, process redesign, reduction of single-use plastics and PPE, etc. Is of utmost importance.

Anticancer Effects of Valproic Acid via Regulation of Epigenetic Mechanisms in Non-small-cell Lung Cancer A549 Cell Line.

Epigenetic mechanisms are the most important factors contributing to both the development and metastasis of cancer cells. We aimed to scrutinize the role of epigenetic alternations of genes involved in cancer metastasis, including CD44v6 (metastasis indicator) and Nm23-H1 (a novel tumor suppressor), in the A549 lung cancer cell line. The A549 cells were cultured in the DMEM medium. Valproic acid (VPA) was used as a histone deacetylase inhibitor. Caspase-3 activity was assessed by adding DEVD-pNA substrate to the cell lysate. Gene expression was determined by real-time PCR. Finally, protein expression was assessed by western blot. The results showed that VA significantly decreased the expression of the CD44v6 gene and its protein level. This was further accompanied by lower expressions of MMP-2 and MMP-9 genes. On the other hand, the expression of Nm23-H1 and its protein were significantly increased in the cells accompanied by higher activity of caspase-3 (P ˂ 0.05). Our results showed that epigenetic regulation of CD44v6, Nm23-H1, MMP-2, and MMP-9 might be involved in the pathogenesis and metastasis of lung cancer. Therefore, the use of histone deacetylase inhibitors can be effective in the suppression of metastases and the treatment of these tumors.

Are history of dietary intake and food habits of patients with clinical symptoms of COVID 19 different from healthy controls? A case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease that put unprecedented significant strain on clinical services and healthcare systems. The aim of the present research was to assess dietary food groups and also food habits of patients with clinical symptoms of COVID 19 and healthy controls. METHODS: This case-control research was carried out on 505 participants (279 subjects with clinical symptoms of COVID-19 and 226 controls), in age 18-65 years. Dietary food group's intake last year was investigated by a food frequency questionnaire. Food habits were asked by a general information questionnaire. The strength of the association between food group's intakes with the odds ratios (ORs) of COVID-19 was assessed using Logistic regression models. RESULTS: After adjusting for physical activity in the logistic regression models, intake of dough and yogurt had a significantly protective role on occurrence of COVID19 (OR = 0.62; 95% confidence interval (CI) = 0.44-0.87; P = 0.006) (OR = 0.74; 95% CI = 0.56-0.98; P = 0.044), respectively. No significant differences were seen in food habits between the two groups in the last year ago. CONCLUSIONS: High risk population for COVID19, advised to consume enough amount of yogurt and dough at the time of this pandemic.

Gallic acid ameliorates sodium arsenite-induced renal and hepatic toxicity in rats.

Chronic exposure to toxic inorganic arsenic results in the adverse health effects including skin lesions, cardiovascular diseases, diabetes, neurological disorders, and liver and kidney diseases. Gallic acid (GA) is an important phenolic compound, which could protect different tissues from oxidative stress induced damage. The present study investigated effects of GA against sodium arsenite (SA)-induced renal and hepatic toxicity. Thirty-five rats were randomly divided in to five groups; group 1 was treated with normal saline (2 ml/kg/day, p.o.; for 21 days); group 2 was exposed to SA (10 mg/kg/day, p.o.; for 14 days); groups 3 and 4 were treated with GA (10 and 30 mg/kg/day, respectively; for 7 days) prior to exposure to SA, and treatment was continued up to 21 days in parallel with SA administration; group 5 was treated with GA (30 mg/kg/day, p.o.; for 21 days). The level of MDA, IL-1ß, NO and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were evaluated in kidney and liver tissues. Histopathological parameters and serum levels of ALT, AST, ALP, Cr and BUN were also assessed. Treatment with GA remarkably improved SA-induced alteration of hematological and histopathological parameters; these protective effects were associated with the reduction of SA-induced elevation of MDA, IL-1ß and NO levels as well as reduction of GSH level and GPx, SOD and CAT activity. Our results suggest that GA may inhibit SA-induced kidney and liver toxicity through scavenging reactive free radicals and increasing intracellular antioxidant capacity.

Protective effects of apigenin on altered lipid peroxidation, inflammation, and antioxidant factors in methotrexate-induced hepatotoxicity.

Methotrexate (MTX) is used as an effective chemotherapeutic agent against autoimmune diseases and tumors. Oxidative stress and inflammation are involved in the pathogenesis of MTX-induced damage. This study aimed at examining the ameliorating effects of apigenin (API) as a natural antioxidant on MTX-induced hepatotoxicity. The rats were classified into four groups: group I: normal saline-treated, group II: MTX-treated (20 mg/kg, ip, single dose at day 7), group III: MTX + API-treated (20 mg/kg, po), and group IV: API-treated. API was administrated for 9 days. Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) were used as biochemical factors of MTX-induced hepatic injury. In hepatic tissues, the levels of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), and activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) as oxidative stress markers along with inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1ß) were assessed. Our results showed that MTX administration significantly increased ALP, ASP, ALT, MDA, NO, TNF-α, and IL-1ß levels and significantly decreased antioxidant factors such as GSH, CAT, GPx, and SOD. The API pretreatment group showed a significant rise in hepatic antioxidant markers, besides significant reductions in the serum levels of AST, ALT, and ALP and hepatic content of MDA, TNF-α, NO, and IL-1ß. In addition, the hepatoprotective effect of API was confirmed by histological evaluation of the liver. API can prevent MTX-induced hepatotoxicity through mitigation of oxidative stress and inflammation.

Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protective Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity.

INTRODUCTION: In multiple studies, involvement of oxidative stress in the pathogenesis of methotrexate (MTX)-mediated liver damage has been confirmed. Use of many drugs has been examined experimentally in order to prevent or diminish oxidative stress. However, no study has yet examined the effects of ferulic acid (FA) on MTX-induced liver damage. This study aimed at evaluating the effects of FA on protection against liver damage induced by MTX in mice. MATERIALS AND METHODS: In this the mice were divided into five groups in a random manner: I) control; II) MTX (20 mg/kg); III and IV) FA (50 and 100 mg/kg) + MTX; and V) FA (100 mg/kg), and we measured serum factors, oxidative stress and inflammatory factors. RESULTS: In the MTX group, accumulation of inflammatory cells, accumulation of red blood cell (RBC), and nuclear pyknosis (NP) were detected in the liver. In line with the histological data, the levels of nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α increased (TNF-α), whereas the reduced glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) content reduced in the MTX group. However, FA ameliorated these hazardous effects in the antioxidant and anti-inflammatory systems in MTX-treated groups. CONCLUSION: Based on our findings, oxidative stress impairment and MTX-induced liver damage were ameliorated following FA pretreatment at both histological and biochemical levels. Therefore, FA can be effectively used in abrogation of MTX-induced toxicity.

Protective effect of alpha-lipoic acid on di-(2-ethylhexyl) phthalate-induced testicular toxicity in mice.

Phthalates are synthetic chemicals, widely used as plasticizers due to their flexibility in plastics. Human populations may be exposed to phthalates through direct contact or environmental contamination. Most studies have focused on the effects of phthalates on the reproductive tract and have classified these compounds as endocrine disruptors. In this study, we aimed to investigate the possible oxidative damage induced by di-(2-ethylhexyl) phthalate (DEHP) in the mouse testis and to evaluate the regulatory effects of alpha-lipoic acid (LA). For this purpose, forty male mice were divided into four experimental groups. Group I received normal saline (2 mL/kg; p.o.) and corn oil (5 mL/kg; p.o.) as the control group, group II received DEHP (2 g/kg; p.o.), group III received DEHP and LA (20 mg/kg; p.o.), and group IV was treated with LA alone; treatments continued for 2 weeks. The glutathione level (GSH), as well as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities, was determined in mice. In addition, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were measured. Nitric oxide (NO) level, malondialdehyde (MDA) level, sperm characteristics, and histological changes of the testes were also evaluated. The results showed that 2 g/kg of DEHP could significantly decrease the sperm motility. Based on our findings, DEHP significantly reduced the production and count of sperms; these toxic effects were associated with alterations in the serum hormone levels. In the DEHP group, a significant reduction was reported in the serum testosterone, FSH, and LH levels. LA improved DEHP-induced changes in hormonal levels and sperm index. According to our findings, treatment with DEHP triggered histopathological changes and oxidative stress, which were normalized by LA pretreatment. In conclusion, DEHP disrupts the testicular function in rats, at least partly through induction of oxidative stress. On the other hand, LA exhibits potential protective effects on testicular toxicity induced by DEHP.

Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats.

BACKGROUND: Methotrexate (MTX) is used commonly in the treatment of various cancers and inflammatory diseases; nevertheless, the associated hepatotoxicity has limited its clinical application. Crocin (CRO) is described as a natural carotenoid with analgesic, antioxidant, and antiinflammatory properties. This study aimed to determine the effects of CRO on MTX-induced hepatotoxicity. METHODS: For pretreatment, CRO at doses of 25 and 50 mg/kg (po), as well as 20 mg/kg (ip) of MTX, was injected in rats. RESULTS: MTX led to hepatotoxicity, as confirmed by the significant increase in liver markers, histopathological changes, decreased GSH content, and reduced antioxidant enzyme activity (i.e., CAT, SOD, and GPx). It increased TNF-α, IL-1ß, lipid peroxidation, and nitric oxide levels. Nevertheless, by increasing antioxidant defense in hepatic tissues and reducing oxidative stress and proinflammatory mediators, pretreatment with CRO could alleviate hepatotoxicity. CONCLUSION: CRO can inhibit MTX-induced hepatotoxicity through improving antioxidant defense and reducing oxidative stress and inflammation.

Ameliorative effect of gallic acid on sodium arsenite-induced spleno-, cardio- and hemato-toxicity in rats.

AIM: Arsenic is an important toxic chemical affecting millions of people around the world. Exposure to inorganic arsenic results in various health problems including skin lesions, hypertension, hematological disturbance, cardiovascular disease, spleen enlargement and cancer. Gallic acid (GA) is an important phenolic compound possessing various pharmacological properties including anti-inflammatory, antioxidant and free radical scavenging activities. The present study investigated effects of GA against sodium arsenite (SA)-induced spleno-, cardio- and hemato-toxicity. MAIN METHODS: Thirty-five adult male Wistar rats were randomly divided into five groups; group I received normal saline (2 ml/kg/day, p.o.) for 21 days, group II received SA (10 mg/kg/day, p.o.) for 14 days, group III and IV were treated with GA (10 and 30 mg/kg/day, respectively) for 7 days prior to receive SA and treatment was continued up to 21 days in parallel with SA administration, group V received GA (30 mg/kg/day, p.o.) for 21 days. The level of MDA, NO and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase were measured in heart and spleen tissues. Creatine kinase-MB (CK-MB) activity and hematological and histopathological parameters were also assessed. KEY FINDINGS: GA significantly decreased SA-induced elevation of MDA and NO levels and reduction of GSH level and GPx and SOD activity in heart and spleen tissues. Furthermore, GA improved SA-induced alteration in hematological and histopathological parameters and reduced SA-induced elevation of serum CK-MB activity. SIGNIFICANCE: Our results suggest that GA inhibits SA-induced spleno-, cardio- and hemato-toxicity through reducing oxidative stress.

Effect of gemfibrozil on cardiotoxicity induced by doxorubicin in male experimental rats.

Cardiotoxicity is an adverse effect of the anticancer drug doxorubicin (DOX). Gemfibrozil (GEM) is a lipid-lowering drug with a number of biological properties such as anti-inflammatory and antioxidant activities. Therefore, we decided to investigate the effect of GEM on DOX-induced cardiotoxicity in rats. Twenty-eight adult male Wistar rats were divided into four experimental groups as follows: Group I received normal saline (2 ml/kg) orally for 14 days, group II received DOX (2.5 mg/kg; in six injections; accumulative dose: 15 mg/kg) intraperitonially for 14 days, group III received DOX + GEM (100 mg/kg) orally for 14 days concomitantly with DOX administration, and group IV received GEM orally for 14 days. Lipid panel, various biochemical biomarkers, and histological observations were evaluated in serum and heart samples. According to our results, DOX significantly increased the levels of lipid panel (triglycerides, total cholesterol, and low-density lipoproteins cholesterol) as well as markers of cardiac dysfunction (Aspartate aminotransferase, Creatine kinase-muscle/brain, Lactate dehydrogenase and Cardiac Troponin I). Moreover, DOX significantly increased malondialdehyde and nitric oxide levels in cardiac tissue. Furthermore, administration of DOX reduced the level of glutathione as well as the superoxide dismutase, catalase, and Glutathione peroxidase activities. DOX-treated rats showed significantly higher tumor necrosis factor-α and interleukin-1ß. GEM administration significantly attenuated the lipid panel and biochemical biomarkers in DOX-treated rats. Our results were confirmed by histopathological evaluations of the heart. Based on our findings, GEM is a promising cardioprotective agent in patients treated with DOX through mitigative effects on biochemical markers and oxidative stress indices.

Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats.

The major side effect of gentamicin (GEN) is nephrotoxicity which in turn restricts the clinical use of this drug. In this study, the effect of gallic acid (GA) on gentamicin-induced nephrotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups: control, GEN (100 mg/kg/day), GEN + GA (30 mg/kg/day), GA (30 mg/kg/day). All drug administrations were done intraperitoneally (i.p) for eight consecutive days. Twenty-four hours after the last administration, blood samples were collected to determine serum creatinine (Cr), blood urea nitrogen (BUN). The right kidney was used for histological examination. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were assayed in left renal tissue. Results showed a significant increase in the levels of MDA, NO, Cr, and BUN and decrease of GSH, CAT, GPx, and SOD by GEN administration. Co-administration with GA showed reduction in the levels of MDA, NO, Cr, and BUN and increase in GSH, CAT, GPx, and SOD. Also, the nephroprotective effect of GA was confirmed by the histological examination of the kidneys. The results of our study showed that GA exerts a significant nephroprotective effect against GEN-induced nephrotoxicity.