Toxicity In Male Rats Research Articles

Ethyl acetate fraction of Spathodea campanulata (Bignoniaceae) attenuates lead acetate induced testicular toxicity in male Wistar rats.

The use of Spathodea campanulata in folklore medicine for the management of reproductive disorders has been poorly reported. We sought to investigate the protective potential of the ethyl acetate fraction of S.campanulata stem bark extract (EFSC) on lead acetate-induced (LA) testicular toxicity in male rats. Animals during a 28days treatment received dimethyl sulfoxide (DMSO, 0.1%), LA (20mg/kg), and EFSC (200mg/kg). Others received EFSC only (100, 200, and 400mg/kg) or vitamin E (100mg/kg) 1h prior to LA (20mg/kg) administration. LA administration decreased sperm counts and motility by 36.39 and 40.69% respectively in rats. Also, LA-untreated rats showed elevated malondialdehyde (MDA) and decreased total proteins in testis (260, 33%) and epididymis (62, 29%) respectively. However, EFSC (100, 200, or 400mg/kg) administrations improved sperm morphological characteristics as well as antioxidant status in LA-treated rats. EFSC (400mg/kg) showed improved testis seminiferous tubules that were almost normal in the LA-treated rats. Further, EFSC contains a high 9-octadecenoic acid methyl ester. Overall, evidence by LA-induced testicular toxicity, EFSC provides chemopreventive roles via antioxidant mechanisms.

Review Study of Antioxidants and the Cinnamon Oil Effects

The aim of the study to estimate the antioxidant action and protecting effect of ethanolic cinnamon extract against CCl4 induced toxicity in male rats. To determine the effect of different concentrations of ethanolic cinnamon extract on male rats that fed a high cholesterol diet that induced hyperlipidemia. The experiment has been conducted in the present study., aimed to evaluate the hepatoprotective, role of Cinnamomum zeylanicum ethanolic extract in carbon tetrachloride (CCl4) induced hepatotoxic male rats, The cinnamon and its oil reported to have many beneficial uses in food preservation due to antioxidant of cinnamon. The Phenolic compounds extracted from cinnamon such as hydroxyl cinnamaldehyde and the hydroxycinnamic acid act as scavengers of peroxide radicals and avoid oxidative damage (Mathew and Abraham, 2006; Leela, 2008). Ranjbar et al, (2006) observed individuals consuming cinnamon tea showed increased total serum antioxidant status, increased thiols such as glutathione, NADPH, NADH, SOD, and decreased lipid peroxidation.

Ameliorative effect of Alpinia officinarum Hance extract on nonylphenol-induced reproductive toxicity in male rats.

Nonylphenol (NP), an endocrine-disrupting chemical, interferes with reproductive function and induces oxidative stress in different organs, including the testis and prostate. Alpinia officinarum Hance (ALP), a plant species of the Zingiberaceae family, has proven antioxidant properties. This study aimed to evaluate the effect of the alcoholic extract of ALP treatment on NP-induced reproductive toxicity and oxidative stress in male rats using biochemical and histopathological biomarkers. Our experimental groups were defined as follows: oil treatment (control), NP 10mg/kg, ALP 10mg/kg (ALP HD), NP+ALP 5mg/kg (NP+ALP LD) and NP+ALP 10mg/kg (NP+ALP HD). NP administration caused significant cytotoxicity and a significant increase in oxidative stress prostate-specific antigen (PSA) levels accompanied by a significant reduction in testosterone levels. The relative weight of the testis of both NP+ALP LD and NP+ALP HD groups was significantly decreased compared to the control group. Histopathological evaluations revealed destructive effects in testis and prostate tissue samples. In conclusion, ALP administration improved cytotoxicity, oxidative stress, testosterone and PSA levels, and testis and prostate tissue destructive effects induced by the NP in male rats.

Дія L-глутамінової кислоти на зміни біохімічних показників щурів, інтоксикованих тетрахлорметаном

This study aims to explore the ameliorative effects of L-glutamic acid (L-Glu) against carbon tetrachloride (CCl4) toxicity in male rats. Changes in the activities of alanine and aspartate aminotransferases (ALAT, ASAT) were studied in the tissues and blood of rats. Concentrations of creatinine, triacylglycerol and cholesterol were also determined in the blood of experimental animals. Intraperitoneal administration of CCl4 to rats led to changes in the blood of animals of the studied parameters — an increase of the activities of aminotransferases, triacylglycerol and cholesterol levels. At the same time, a decrease of ALAT activity was observed in the tissues of the myocardium and spleen of intoxicated animals, ASAT in their brain, and in the tissues of the lungs there was an increase in the activity of ALAT and the growth of ASAT in the tissues of the spleen In turn, with additional administration to animals intoxicated with tetrachloromethane L-Glu mitigation or no change in most of the studied indicators was observed, namely, in the blood the activity of ASAT fluctuated within the control values, and the concentrations of triacylglycerol and cholesterol did not change compared to the control. Also under the action of the studied aminoacid, no changes were detected in the activities of ALAT in lung tissue and ASAT in spleen tissue. The obtained results indicate a corrective effect of L-Glu on the physiological and biochemical parameters of rats in their intoxication with carbon tetrachloride.

Study on baicalin on liver and kidney toxicity in male rats

Objective: To observe the toxic effects of different doses of baicalin on liver and kidney of rats after different time administration, and provide experimental reference for the safety of clinical medication. Methods: In April 2019, 42 Wistar male rats were randomly divided into a control group (0.9% sodium chloride solution) and baicalin administration groups (100, 200 mg/kg) , 14 rats in each group, and one was given by oral gavage. 7 times/d, 6 times/week, 7 rats in each group were sacrificed 28 and 56 days after the administration. The wet weights of liver and kidney were weighed and the organ coefficients were calculated. The hematoxylin-eosin (HE) staining was used to detect the histomorphological changes. And the levels of serum alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , alkaline phosphatase (ALP) , blood urea nitrogen (BUN) and creatinine (CRE) were detected. Results: After 56 days of administration in baicalin 200 mg/kg rats, the body weight and kidney coefficient were lower than those of the control group. Histopathology showed that glomerular atrophy became smaller, renal tubules were significantly atrophied, and epithelial cell necrosis occurred. No obvious abnormalities in liver was observed. After 56 days of administration in baicalin 200 mg/kg rats, the levels of BUN and CRE in the serum were higher than those of the control group, and the differences were statistically significant (P<0.05) . There were no obvious abnormalities in the baicalin 100 mg/kg group and the 28 d of administration in baicalin 200 mg/kg group. Conclusion: Under the conditions of this test, baicalin has certain renal toxicity in male rats.

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

Cisplatin (CIS)-induced testicular injury is a major obstacle in its application as antineoplastic agent. In this study, we investigated the protective effect and mechanism of roflumilast (ROF), a PDE4 inhibitor, against CIS-induced testicular toxicity in rats. Besides, the cytotoxic effect of CIS, with and without ROF, was evaluated on PC3 cell line. ROF reversed CIS-induced abnormalities in sperm characteristics, normalized serum testosterone level, and ameliorated CIS-induced alterations in testicular and epidydimal weights and restored normal testicular structure. Moreover, ROF increased intracellular cAMP level, PKA and HO-1 activities and Nrf2, NQO-1 and HO-1 gene expression, improved testicular oxidative stress parameters (TBARS, NO, GSH levels, and CAT activity) and inflammatory mediators (IL-1β and TNF-α, and NF-κβ p65gene expression) and reduced the proapoptotic proteins, caspase-3, Bax and increased Bcl-2. Lastly, in vitro analyses showed that ROF augmented the anticancer efficacy of CIS and enhanced the increase in gene expression of Nrf2, HO-1, and NQO-1 and the inhibition of gene expression of NF-κβ p65 induced by CIS and enhanced its apoptotic effect in PC3 cells. Conclusively, PDE4 inhibition with induction of Nrf2/HO-1, NQO-1 is a potential therapeutic approach to protect male reproductive system from the detrimental effects with augmenting, the antineoplastic effect of CIS.

N-acetyl cysteine co-treatment abates perfluorooctanoic acid-induced reproductive toxicity in male rats.

Perfluorooctanoic acid is a synthetic perfluoroalkyl-persistent in the environment and toxic to humans. N-acetylcysteine is a pro-drug of both amino acid l-cysteine and glutathione-a non-enzymatic antioxidant. N-acetylcysteine serves as an antidote for paracetamol poisoning and alleviates cellular oxidative and inflammatory stressors. We investigated N-acetylcysteine role against reproductive toxicity in male Wistar rats (weight: 140-220g; 10weeks old) posed by perfluorooctanoic acid exposure. Randomised rat cohorts were dosed both with perfluorooctanoic acid (5mg/kg; p.o) or co-dosed with N-acetylcysteine (25 and 50mg/kg p.o) for 28days. Sperm physiognomies, biomarkers of testicular function and reproductive hormones, oxidative stress and inflammation were evaluated. Co-treatment with N-acetylcysteine significantly (p<.05) reversed perfluorooctanoic acid-mediated decreases in reproductive enzyme activities, and adverse effect on testosterone, luteinising and follicle-stimulating hormone concentrations. N-acetylcysteine treatment alone, improved sperm motility, count and viability, and reduced total sperm abnormalities. Co-treatment with N-acetylcysteine mitigated perfluorooctanoic acid-induced alterations in sperm function parameters. N-acetylcysteine abated (p<.05) perfluorooctanoic acid-induced oxidative stress in experimental rats testes and epididymis, and generally improved antioxidant enzyme activities and cellular thiol levels. Furthermore, N-acetylcysteine suppressed inflammatory responses and remedied perfluorooctanoic acid-mediated histological injuries in rat. Cooperatively, N-acetylcysteine enhanced reproductive function in perfluorooctanoic acid dosed rats, by lessening oxidative and nitrative stressors and mitigated inflammatory responses in the examined organ.

Ameliorative effect of L-carnitine on chronic lead-induced reproductive toxicity in male rats.

Lead toxicity is one of the causative agents of male infertility that raised concern from environmental contamination worldwide. L‐carnitine, a biologically active amino acid, present in high concentration in the reproductive organs such as the epididymis, is involved in sperm maturation. The possible protective effect of L‐carnitine in experimentally lead‐induced male reproductive toxicity in rats was evaluated in this study. Thirty adult male Wistar rats were divided into three groups. Group 1: the negative control group was treated with normal saline; Group 2: exposed to 50 mg/kg lead acetate (2% solution in saline); and Group 3: treated with lead acetate 50 mg/kg (2% solution in saline) + L‐carnitine 100 mg/kg. At the end of the experimental period, body and testicular weights were determined, blood samples were withdrawn for hormonal assays of FSH, LH and testosterone. Sperm parameters as sperm count, morphology, viability and motility were measured. Testicular tissue homogenates were prepared for enzymatic assays and for measuring oxidative stress parameters. Lead significantly increased both oxidative stress and the concentration of lactate dehydrogenase‐C in the testicular tissues with a decrease in sperm count, motility and viability. Lead acetate treatment, induced alteration in sperms with normal morphology together with reductions in the serum FSH, LH, testosterone, body and testicular weights. The concentration of 17β‐hydroxysteroid dehydrogenase was significantly reduced. Co‐administration of L‐carnitine significantly reduced testicular oxidative stress, improved sperm parameters, elevated serum FSH, LH and testosterone with an insignificant reduction in the testicular weight. The concentrations of 17β‐hydroxysteroid dehydrogenase and lactate dehydrogenase‐C were significantly improved by L‐carnitine. The overall results indicate that L‐carnitine is expected to improve the lead acetate‐induced male reproductive toxicity.

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats.Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats.

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.

Detoxification gene expression, genotoxicity, and hepatorenal damage induced by subacute exposure to the new pyrethroid, imiprothrin, in rats.

The pyrethroid imiprothrin is widely used worldwide for control of insects in the agriculture and public health sectors. No sufficient information is however available concerning detoxification gene expression, i.e., cytochrome P450 1A2 (CYP1A2) and metallothionein 1a gene, oxidative stress, lipid peroxidation, DNA damage, cytotoxicity, genotoxicity, and organ injury induced by imiprothrin in mammals. This study is designed to explain the mechanism of imiprothrin induced detoxification gene expression, DNA damage, cytotoxicity, genotoxicity, and organ toxicity in male rats. The benchmark dose (BMD) was calculated to find the best sensitive markers to imiprothrin toxicity. Imiprothrin was injected intraperitoneally (i.p.) into male rats once a day for 5 days with doses of 19, 38, and 75 mg/kg body weight (b.wt.). Imiprothrin caused a significant increase in lipid peroxidation and changes in oxidative stress biomarkers in treated rats. Significant dose-dependent changes in the liver and kidney biomarkers were observed. Histopathological alterations were seen in the liver and kidney tissue of male rats. Imiprothrin also significantly increased chromosomal aberrations (CA) and micronuclei in bone-marrow cells, and induced lipid peroxidation, oxidative stress, cytotoxicity, and liver and kidney dysfunction, and damage. Imiprothrin induced DNA damage and over detoxification gene expression of CYP1A2 and metallothionein 1a gene in hepatocytes of male rats. Imiprothrin thus shows clastogenic and genotoxic potential. The mechanism for hepatorenal toxicity and injury, genotoxicity/cytotoxicity of imiprothrin might be due to enhanced lipid peroxidation, and oxidative stress associated with overproduction of free radicals, especially reactive oxygen species, and an imbalance in redox status. From the BMD models, aspartate aminotransferase (AST), total protein, uric acid, superoxide dismutase (SOD), and micronuclei (MPEs) were very sensitive markers to imiprothrin toxicity.

Olanzapine induced reproductive toxicity in male rats

Although it is reported that olanzapine (OLZ), which is an atypical antipsychotic drug, causes sexual dysfunction in men, it is noteworthy that there is not any study evaluating the toxic effects of OLZ on the male reproductive system. In the scope of this research, it was aimed to assess the reproductive toxic effects of OLZ by oral administration of 2.5, 5, or 10 mg/kg of it to male rats for 28 days. For this purpose, sperm concentration, motility and morphology, and DNA damage were determined, and histopathological examination of testis tissue was carried out in rats. Also, the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, which play roles in the regulation of reproductive functions, and the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) which play roles in reproductive pathologies as oxidative stress biomarkers, were determined. According to the results, normal sperm morphology was decreased in 5 ve 10 mg/kg OLZ-administered groups, and pathological findings were evident in the testicular structure of the OLZ-administered group when compared with the control group. It was determined that serum LH, FSH, and testosterone levels were decreased in the OLZ-administered group. Also, decreases of GSH levels in testis tissue were determined and evaluated as the markers of the oxidative stress induced by OLZ in the testis. In conclusion, it was determined that reproductive toxic effects were induced in rats by OLZ administration. This pathology was accompanied by alterations of the hormone levels and testicular oxidative stress.

Potential anti-toxic effect of d-ribose-l-cysteine supplement on the reproductive functions of male rats administered cyclophosphamide.

This study aimed to access the protective effects of d-ribose-l-cysteine (DRLC) on cyclophosphamide (CPA) induced gonadal toxicity in male rats. Forty-eight male Sprague-Dawley rats were divided into six groups of eight rats each. Group I the control, received distilled water (10ml/kg), Group II received a single dose of CPA 100mg/kg body weight intraperitoneally (i.p), Groups III and IV received a single dose of CPA at 100mg/kg (i.p) and then were treated with DRLC at 200mg/kg bodyweight (b.w) and 400mg/kg b.w for 10days, respectively. Rats in Groups V and VI received DRLC at 200 and 400mg/kg b.w for 10days, respectively. DRLC was administered orally. Results showed that CPA increased percentage of abnormal sperm cells and reduced body weight, sperm count, sperm motility, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels (p<0.05). CPA also induced oxidative stress as indicated by the increased malondialdehyde (MDA) content and reduced activities of the oxidative enzymes measured (p<0.05). Liver enzymes were elevated while the blood cells production was decreased in the rats administered CPA. DRLC supplementation enhanced the antioxidant defence system as indicated in the reduced MDA levels and increased activities of the antioxidant enzymes when compared with CPA (p<0.05). Bodyweight, sperm count, sperm motility, FSH, and testosterone levels were increased in the CPA+DRLC II group compared with CPA (p<0.05). The results of this present study showed that DRLC has a potential protective effect on CPA-induced gonadotoxicity.

Chlorogenic acid co-administration abates tamoxifen-mediated reproductive toxicities in male rats: An experimental approach.

Reports over the years have demonstrated toxic side effect-including reproductive toxicity- of tamoxifen (TAM), a drug of choice in the management of primary breast cancer. Chlorogenic acid (CGA), a dietary polyphenol, reportedly elicits beneficial pharmacological effects. However, the impact of CGA on TAM-associated reproductive toxicity is absent in the literature. We, therefore, experimented on CGA's effect and TAM-mediated reproductive toxicity in rats. Cohorts of rats were treated with TAM (50mg/kg) or co-treated with CGA (25 or 50mg/kg) for 14 consecutive days. The result showed that treatment of CGA significantly increases testosterone, LH, and FSH levels compared to the TAM group. However, prolactin level was markedly decreased after pretreatment of CGA in TAM-treated rats. CGA abated TAM-induced decreases acid phosphatase, alkaline phosphatase, and antioxidant enzymes in the testis. CGA alleviated TAM-facilitated surges of reactive oxygen and nitrogen species, myeloperoxidase, nitric oxide, interleukin-1β, and tumor necrosis factor-alpha in rats epididymis and testes. Additionally, CGA increased anti-inflammatory cytokine -interleukin-10-, suppressed caspase-3 activity, and reduced pathological lesions in the examined organs of rats co-treated with CGA and TAM. CGA phytoprotective effect improved reproductive function occasioned by TAM-mediated toxicities in rats, by abating oxido-inflammatory damages and downregulating apoptotic responses. PRACTICAL APPLICATIONS: CGA protects against the damaging oxido-inflammatory responses incumbent on TAM metabolism. As an antioxidant abundant in plant-derived foods, CGA reportedly protects against inflammatory damage, hypertension, and neurodegenerative diseases. We present evidence that CGA ameliorates TAM-induced reproductive dysfunction by suppressing oxidative and inflammation stress downregulate apoptosis and improve reproductive function biomarker in rats.

Phytochemical and Biological Evaluation of a Newly Designed Nutraceutical Self-Nanoemulsifying Self-Nanosuspension for Protection and Treatment of Cisplatin Induced Testicular Toxicity in Male Rats.

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.

Green coffee methanolic extract and silymarin protect against CCl4-induced hepatotoxicity in albino male rats

BackgroundDuring the last few decades, patients worldwide have been interested in using alternative medicine in treating diseases to avoid the increased side effects of chemical medications. Green coffee is unroasted coffee seeds that have higher amounts of chlorogenic acid compared to roasted coffee. Green coffee was successfully used to protect against obesity, Alzheimer disease, high blood pressure and bacterial infection.MethodsThis study aimed to investigate the probable protective activity of the green coffee methanolic extract, silymarin and their combination on CCl4-induced liver toxicity in male rats. Thirty Sprague – Dawley male albino rats were divided into 5 groups; control negative (G1) just got the vehicle (olive oil) and the other four groups received CCl4 dissolved in olive oil through an intraperitoneal injection and were divided into untreated control positive group (G2), the third group (G3) was treated with green coffee methanolic extract, the fourth group (G4) was treated with silymarin, and the fifth group (G5) was treated with a combination of green coffee methanolic extract and silymarin.ResultsIn the positive control group treated with CCl4 (G2), the CCl4-induced toxicity increased lipid peroxidation, IL-6, kidney function parameters, liver function enzymes, total cholesterol, triglycerides and low-density lipoproteins, and decreased irisin, antioxidants, CYP450 and high-density lipoprotein levels. Hepatic tissues were also injured. However, treating the injured rats in G3, G4 and G5 significantly improved the altered parameters and hepatic tissues.ConclusionsGreen coffee methanolic extract, silymarin, and their combination succeeded in protecting the male rats against CCl4 hepatotoxicity due to their antioxidant activity. Effect of green coffee methanolic extract mixed with silymarin in G5 was more efficient than that of green coffee methanolic extract in G3 or silymarin in G4.

Spirulina ameliorates arsenic induced reproductive toxicity in male rats.

Spirulina (Spirulina platensis), has numerous health benefits including antioxidant, immunomodulatory, and anti-inflammatory activities, works against heavy metal toxicity, and is often used as a food supplement in human, animals, birds and fishes. This study aimed to evaluate the protective ability of the dietary spirulina against the toxic effects of inorganic arsenic (iAs) on male reproductive parameters in rats. Seventy-two mature Long-Evans male rats, dividing into six groups (T0, T1, T2, T3, T4 and T5) (12 rats/group) were included in this study. The T3, T4 and T5 group rats were treated with three consecutive doses (1.0 g, 1.5 g and 2.0 g/kg feed) of spirulina in feed along with 3.0 mg NaAsO2/kg body weight (BW) in drinking water (DW) daily for 90 days. Each rat of group T1 received NaAsO2 (3.0 mg/kg BW) in DW, and those of T2 group were fed with spirulina (2.0 g/kg feed) daily for 90 days. The rats of group T0 served as the control with normal feed and water. Total arsenic (tAs) contents, reproductive parameters (testicular weight, sperm motility and morphology), and histological changes in the testicles were evaluated in these rats. Arsenic dosing significantly (p=0.003, Kruskal-Wallis test) increased the tAs contents in the testicles, decreased testes weight, sperm morphology and motility compared to the controls. The effect of arsenic dosing was also evidenced by the histological changes like decreased germinal layers in the seminiferous tubules of the treated rats. Moreover, dietary spirulina (2.0 g/kg feed) supplementation significantly (p=0.011, Kruskal-Wallis test) lowered tAs contents in testicles and increases testes weights, sperm motility and morphology. Therefore, spirulina can be used as an effective dietary supplement to ameliorate the adverse effects of arsenic induced reproductive toxicities. However, further study is required to elucidate the underlying molecular mechanisms of reduction of arsenic induced reproductive toxicity by spirulina.

Antioxidant, anti-inflammatory and protective potential of gallic acid against paraquat-induced liver toxicity in male rats.

Objective:As a herbicide, paraquat is a toxic agent that has devastating effects on human health. Gallic acid, on the other hand, is a natural compound that its anti-oxidant values have been reported in previous studies. Given these, this study was designed to evaluate whether gallic acid could reduce the toxic effects of paraquat in the liver of rats.Materials and Methods:Six groups of rats were considered in this study. Group 1 (control group), group 2 (25 mg/kg of paraquat), group 3 (paraquat-plus-silymarin), and groups 4, 5, and 6 (paraquat together with gallic acid at the doses of 25, 50, and 100 mg/kg, respectively). After treatment, biochemical, oxidative, and histopathological parameters were evaluated in the rats.Results:We found that as compared to the control group, while paraquat reduced the hepatic levels of anti-oxidative compounds such as vitamin C (p<0.001), superoxide dismutase (SOD) (p<0.001), and catalase (CAT) (p<0.001), the toxic agent increased the serum levels of protein carbonyl (PC) (p<0.001), malondialdehyde (MDA) (p<0.05), and IL-1β (p<0.001). Paraquat also increased (p<0.05) both serum lipid profile and liver-associated markers in the rats. Nevertheless, gallic acid not only enhanced (p<0.05) the activity of vitamin C, SOD, and CAT but also remarkably reduced (p<0.05) the serum lipid profile, as well as the oxidative and inflammatory markers in the paraquat-treated rats. Gallic acid had also ameliorating effects on the damaged morphology of hepatocytes upon paraquat treatment.Conclusion:The results of this study suggested that gallic acid possesses reinforcing effects on the antioxidant defense system and could be administered to reduce the toxicity of paraquat.

Orange fruit (Citrus sinensis) peel extract attenuates chemotherapy-induced toxicity in male rats

Background: Cyclophosphamide (CYP) is a chemotherapy drug widely used in the treatment of several types of cancers and autoimmune disorders. Unfortunately, it causes severe side effects on many organs due to its oxidative stress effect. Objective: The present study aims to tentatively identify the phytochemical constituents of orange fruit (Citrus sinensis) peel extract (OFPE) and elucidate the chemopreventive effects of OFPE on CYP drug induced organ toxicity. Methods: The high performance liquid chromatography coupled with mass spectroscopy (HPLC-MS/MS) technique was used to identify the compounds. Thirty-five male rats were divided into five groups (GP; n = 7): GP1: normal control, GP2: OFPE 0.5 only, GP3: CYP-only, GP4: OFPE 0.25 + CYP, and GP5: OFPE 0.5 + CYP. Results: Twenty-nine compounds of polyphenolic nature, mainly flavonoids, anthocyanidins, phenolic acids and limonoids were characterized by HPLC-MS/MS analysis. Among these compounds, naringin, hesperidin, diosmin, rutin, neohesperidin and limonin were the predominant compounds in the examined extract. Serum cellular markers were found to be decreased significantly upon treatment with OFPE (especially high dose). Also, a significant prophylactic effect against liver, kidney, and heart injuries induced by CYP via decreasing inflammation (serum TNF-α, IL-1β & IL-6) and lipid peroxidation (MDA) was also revealed. Also, an increase in antioxidant levels (serum TAO, and cellular GSH & CAT in tissue homogenates) confirmed the protective efficacy of OFPE against CYP toxicity. Conclusions: The present study reveals some chemopreventive properties and beneficial effects of OFPE on CYP-induced organ toxicity via its antioxidant status and immunoregulatory activities.

Development of health-based environmental screening levels for insensitive munitions constituents

Dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ) are constituents of insensitive munitions being developed to minimize the acute hazards associated with non-intentional detonation of warheads. Although a reference dose (RfD) has been established for NQ and occupational exposure levels have been developed for all three compounds, current state-of-the science methods were not used. Here we present the latest toxicity data and interpretations for NTO, DNAN, and NQ and use Bayesian Benchmark Dose modeling and a Bayesian approach to applying uncertainty factors to derive tolerable daily intake (TDI) values. A TDI of 0.02 mg/kg-d was calculated for DNAN based on extramedullary hematopoiesis in female rats. A TDI of 2.4 mg/kg-d was derived for NTO based on testicular toxicity in male rats. A TDI of 4.0 mg/kg-d was derived for NQ based on increased fetal resorptions in rabbits. These TDIs are generally an order of magnitude higher than previously developed reference values. These values can be used to inform public health, occupational safety, and product acquisition and stewardship decisions. Drinking water, soil, and tap water screening levels were derived for residential and worker exposure scenarios to help inform risk assessment decisions.