Damage In Male Mice Research Articles

Role of TRPM8 Channels in Altered Cold Sensitivity of Corneal Primary Sensory Neurons Induced by Axonal Damage.

The cornea is extensively innervated by trigeminal ganglion cold thermoreceptor neurons expressing TRPM8 (transient receptor potential cation channel subfamily M member 8). These neurons respond to cooling, hyperosmolarity and wetness of the corneal surface. Surgical injury of corneal nerve fibers alters tear production and often causes dry eye sensation. The contribution of TRPM8-expressing corneal cold-sensitive neurons (CCSNs) to these symptoms is unclear. Using extracellular recording of CCSNs nerve terminals combined with in vivo confocal tracking of reinnervation, Ca2+ imaging and patch-clamp recordings of fluorescent retrogradely labeled corneal neurons in culture, we analyzed the functional modifications of CCSNs induced by peripheral axonal damage in male mice. After injury, the percentage of CCSNs, the cold- and menthol-evoked intracellular [Ca2+] rises and the TRPM8 current density in CCSNs were larger than in sham animals, with no differences in the brake K+ current IKD Active and passive membrane properties of CCSNs from both groups were alike and corresponded mainly to those of canonical low- and high-threshold cold thermoreceptor neurons. Ongoing firing activity and menthol sensitivity were higher in CCSN terminals of injured mice, an observation accounted for by mathematical modeling. These functional changes developed in parallel with a partial reinnervation of the cornea by TRPM8(+) fibers and with an increase in basal tearing in injured animals compared with sham mice. Our results unveil key TRPM8-dependent functional changes in CCSNs in response to injury, suggesting that increased tearing rate and ocular dryness sensation derived from deep surgical ablation of corneal nerves are due to enhanced functional expression of TRPM8 channels in these injured trigeminal primary sensory neurons.SIGNIFICANCE STATEMENT We unveil a key role of TRPM8 channels in the sensory and autonomic disturbances associated with surgical damage of eye surface nerves. We studied the damage-induced functional alterations of corneal cold-sensitive neurons using confocal tracking of reinnervation, extracellular corneal nerve terminal recordings, tearing measurements in vivo, Ca2+ imaging and patch-clamp recordings of cultured corneal neurons, and mathematical modeling. Corneal nerve ablation upregulates TRPM8 mainly in canonical cold thermoreceptors, enhancing their cold and menthol sensitivity, inducing a rise in the ongoing firing activity of TRPM8(+) nerve endings and an increase in basal tearing. Our results suggest that unpleasant dryness sensations, together with augmented tearing rate after corneal nerve injury, are largely due to upregulation of TRPM8 in cold thermoreceptor neurons.

THE EFFECT OF EXTRACT OF DATE PALM FRUIT (PHOENIX DACTYLIFERA L.) ON FERTILITY IN MALE MICE (MUS MUSCULUS L.)

Objective: Date palm is one of the plants that have used empirically to increase fertility. Ethanol induction can cause sperm damage in male mice. Sperm damage is one of the infertility agents. The aim of this study was to observe and determine anti-infertility effects of the ethanol extract of date palm fruit in khalal stage in male mice compared with propolis.Methods: A total of 5 groups were assigned to 1 control and 4 experimental groups. Control group was treated by intraperitoneal administration of ethanol only. Meanwhile, experimental groups was treated by intraperitoneal administration of ethanol induction and oral administration of 140, 280, and 560 mg/kg BW of khalal date fruit extract and 1400 mg/kg BW of propolis for 34 days. At 35th day, the mice were deeply anesthetized with anesthetic ether and sacrificed. Laparotomy was performed to collect sperms from epididymis and testes for determining testis weight to analyze the sperm. The data were analyzed using one-way ANOVA and Duncan’s test.Results: The result of the research showed that there were anti-infertility activity of ethanol extract of date palm fruit in khalal stage (p<0.05) on count, motility of sperm and weight of testes in male white mice toghether with larger doses administration. The optimum activity was accepted by the administration of doses 560 mg/kg BW.Conclusion: Ethanol extract of khalal date fruit and propolis can increase the quality of sperm pervade sperm count, sperm motility, and weight of testes. Ethanol extract of khalal date fruit can increase sperm quality higher than propolis.

THE EFFECT OF EXTRACT OF DATE PALM FRUIT (PHOENIX DACTYLIFERA L.) ON FERTILITY IN MALE MICE (MUS MUSCULUS L.)

Objective: Date palm is one of the plants that have used empirically to increase fertility. Ethanol induction can cause sperm damage in male mice. Sperm damage is one of the infertility agents. The aim of this study was to observe and determine anti-infertility effects of the ethanol extract of date palm fruit in khalal stage in male mice compared with propolis.Methods: A total of 5 groups were assigned to 1 control and 4 experimental groups. Control group was treated by intraperitoneal administration of ethanol only. Meanwhile, experimental groups was treated by intraperitoneal administration of ethanol induction and oral administration of 140, 280, and 560 mg/kg BW of khalal date fruit extract and 1400 mg/kg BW of propolis for 34 days. At 35th day, the mice were deeply anesthetized with anesthetic ether and sacrificed. Laparotomy was performed to collect sperms from epididymis and testes for determining testis weight to analyze the sperm. The data were analyzed using one-way ANOVA and Duncan’s test.Results: The result of the research showed that there were anti-infertility activity of ethanol extract of date palm fruit in khalal stage (p<0.05) on count, motility of sperm and weight of testes in male white mice toghether with larger doses administration. The optimum activity was accepted by the administration of doses 560 mg/kg BW.Conclusion: Ethanol extract of khalal date fruit and propolis can increase the quality of sperm pervade sperm count, sperm motility, and weight of testes. Ethanol extract of khalal date fruit can increase sperm quality higher than propolis.

Malathion induced testicular toxicity and oxidative damage in male mice: the protective effect of curcumin

BackgroundThe organophosphorus (OP) pesticide malathion is a highly neurotoxic compound, leading to cholinergic syndrome. Malathion produces reproductive toxicity.ObjectivesTo investigate the protective effects of curcumin on the testicular toxicity induced in male mice orally administrated with malathion.Materials and methodsForty-eight mature male mice were used. The mice were divided into four groups, 12 mice each, and treated for 4 weeks as follows: the control (G1), curcumin-treated group (G2), malathion-treated group (G3), and the curcumin plus malathion-treated group (G4). At the end of the experiment, the mice were sacrificed and dissected, and tissue samples were obtained and antioxidant parameters were examined. Tissue samples were also histopathologicaly and immunohistochemically assessed. Samples of blood were collected for assessing the levels of serum hormones, namely follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and acetylcholinesterase activity (AChE).ResultsMalathion exposure caused a decrease in serum testosterone and LH levels and antioxidant enzymes (SOD and CAT) and elevation of oxidative stress marker (MDA). Histological changes were as well observed in the form of maturation abnormalities, intratubular necrosis, and inflammatory infiltrate in malathion-treated mice. Co-administration of curcumin with malathion reduced lipid peroxidation (LPO) activity and improved spermatogenesis and increased catalase (CAT), superoxide dismutase (SOD), and testosterone levels.ConclusionThe current study showed that curcumin could ameliorate the elevated concentration of lipid peroxidation products, increase the levels of antioxidative markers, and improve the pathological changes in the testis induced by malathion administration. The capacity of curcumin to work as antioxidant supposedly relates to its structure.

Corrigendum: Genistein Improves Liver Damage in Male Mice Exposed to Morphine.

[This corrects the article DOI: 10.4103/0366-6999.235117].

Genistein Improves Liver Damage in Male Mice Exposed to Morphine.

Background:Morphine is commonly used to treat severe pain. This substance is significantly metabolized in the liver and causes disturbing effects. Genistein is an isoflavone and has antioxidant properties. The aim of this study was to evaluate the effects of genistein against morphine damages on mouse liver.Methods:Between May 2017 and March 2018, 48 male mice were divided into six groups (n = 8 in each group). Various doses of genistein (25 and 50 mg/kg) and morphine plus genistein (25 and 50 mg/kg) were administered intraperitoneally to 48 male mice for 20 consequent days. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum nitric oxide (NO) levels, liver weight, and the diameter of hepatocytes and central hepatic vein were studied and compared using one-way analysis of variance.Results:Morphine administration significantly increased the mean diameter of the central hepatic vein (22.76 ± 1.9 μm vs. 15.04 ± 0.60 μm, χ2 = 21.814, P = 0.001) and hepatocytes (3.03 ± 0.10 μm vs. 1.10 ± 0.05 μm, χ2 = 9.873, P = 0.001) respectively, blood serum NO level (38.00% ± 2.09% vs. 18.72% ± 4.40%, χ2 = 20.404, P < 0.001), liver enzyme level (AST: 111.80 ± 5.10 ng/ml vs. 81.93 ± 2.20 ng/ml, χ2 = 32.201, P < 0.0001; ALT: 45.14 ± 4.10 ng/ml vs. 35.49 ± 2.50 ng/ml, χ2 = 18.203, P < 0.0001; and ALP: 3.28 ± 0.20 ng/ml vs. 2.14 ± 0.10, χ2 = 5.04, P < 0.0001, respectively), and decreased liver weight (18.50 ± 0.90 g vs. 27.15 ± 0.50 g, χ2 = 22.415, P = 0.001) compared to saline group (0.535–0.750, P < 0.0001). However, administration of genistein plus morphine significantly enhanced liver weight (25 mg/kg: 21.15 ± 2.13 g vs. 18.50 ± 0.90 g, χ2 = 19.251, P < 0.0001; 50 mg/kg: 21.20 ± 1.00 g vs. 18.5 ± 0.9 g, χ2 = 19.502, P < 0.0001, respectively) and reduced the mean diameter of hepatocyte (25 mg/kg: 2.17 ± 0.30 μm vs. 3.03 ± 0.10 μm, χ2 = 22.780, P = 0.001; 50 mg/kg: 2.01 ± 0.20 μm vs. 3.03 ± 0.10 μm χ2 = 7.120, P = 0.001, respectively), central hepatic vein (25 mg/kg: 19.53 ± 1.00 μm vs. 22.76 ± 1.90 μm, χ2 = 20.681, P = 0.001; 50 mg/kg: 19.44 ± 1.20 μm vs. 22.76 ± 1.90 μm, χ2 = 18.451, P = 0.001, respectively), AST (25 mg/kg: 95.40 ± 5.20 ng/ml vs. 111.80 ± 5.010 ng/ml, P < 0.0001; 50 mg/kg: 90.78 ± 6.00 ng/ml vs. 111.80 ± 5.10 ng/ml, χ2 = 17.112, P < 0.0001, respectively), ALT (25 mg/kg: 35.78 ± 5.01 ng/ml vs. 45.14 ± 4.10 ng/ml, χ2 = 15.320, P < 0.0001; 50 mg/kg: 33.78 ± 2.60 ng/ml vs. 45.14 ± 4.10 ng/ml, χ2 = 14.023, P < 0.0001, respectively), ALP (25 mg/kg: 2.35 ± 0.30 ng/ml vs. 3.28 ± 0.20 ng/ml, χ2 = 4.101, P < 0.0001; 50 mg/kg: 2.34 ± 0.10 ng/ml vs. 3.28 ± 0.20 ng/ml, χ2 = 2.033, P < 0.0001, respectively), and NO levels (25 mg/kg: 25.92% ± 2.30% vs. 38% ± 2.09%, χ2 = 17.103, P < 0.0001; 50 mg/kg: 24.74% ± 4.10% vs. 38% ± 2.09%, χ2 = 25.050, P = 0.001, respectively) compared to morphine group.Conclusion:It seems that genistein administration might improve liver damages induced by morphine in mice.

Protective effects of camel whey protein against scrotal heat-mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR-gamma signaling pathways.

Elevation of scrotal temperature is one of the most important causes of impaired spermatogenesis and male infertility, but the exact mechanism remains controversial. The present study investigated the impact of camel whey protein (CWP) on the mechanisms of heat stress (HS)-mediated testicular damage in male mice. Exposure to HS was associated with significant increase in the testicular tissues' oxidative stress. Mechanistically, exposure to HS resulted in upregulation of P53 and Nrf2 expressions; downregulation of Bcl2 and PPAR-γ expressions; and induction of testicular Leydig cell hyperplasia. Because Leydig cells produce testosterone up on stimulation with Luteinizing hormone (LH), HS mice also exhibited significant reduction in the serum testosterone levels followed by significant reduction in the percentages of progressively motile sperm and higher percentages of immotile sperm, when compared with those of control mice. Interestingly, treatment of HS mice with CWP significantly restored the levels of ROS and the activities of antioxidant enzymes in the testicular tissues nearly to those observed in control mice. Furthermore, CWP supplemented HS mice exhibited complete restoration of Bcl2, P53, Nrf2, and PPAR-γ expressions; testicular Leydig cell distribution; significant higher levels of testosterone levels; and hence higher percentages of progressively motile sperm and lower percentages of immotile sperm as compared to HS mice. Our findings reveal the protective effects of CWP against testis injury and infertility induced by exposure to HS by rescuing functional Leydig cells. Additionally, the present study has shed light on the molecular mechanisms underlying improved testicular damage following CWP treatment.

Ilex paraguariensis extracts reduce blood glucose, peripheral neuropathy and oxidative damage in male mice exposed to streptozotocin

Ilex paraguariensis (IP) is used for the preparation of stimulant drinks commonly consumed in South America. Extracts of this plant are known to contain a wide variety of polyphenols, exerting beneficial effects as antioxidant. The aim of this study was to evaluate for the first time the effect of yerba mate extracts in a model of type 1 diabetes induced by streptozotocin (STZ) in mice. We evaluated extract compounds, glucose levels, serum transaminases, and fructosamine in blood, and oxidative stress parameters in liver, kidney and brain. Finally, we analyzed the thermal sensitivity as an indicator of diabetic neuropathy. Ilex paraguariensis extracts reduced hyperglycemia, normalized oxidative stress parameters and prevented peripheral neuropathy. Altogether, these effects can be attributed to the potent antioxidant capacity of IP combined with its potential hypoglycemic effect. We suggest that IP compounds may help to design therapeutic alternatives for the treatment of diabetes mellitus.

In vivo antimutagenic and antiatherogenic effects of the (1 → 3)(1 → 6)-β-d- glucan botryosphaeran

The antimutagenic effect of botryosphaeran, an exocellular (1 → 3)(1 → 6)-β-d-glucan, from the ascomyceteous and plant-borne endophytic fungus, Botryosphaeria rhodina MAMB-05, was evaluated in young (6–8 weeks) and elderly (18 months) Swiss albino mice of both genders. The hypolipidemic, hypoglycemic and antiatherogenic potential was also evaluated in 18-month old male LDL receptor knockout (LDLr−/−) mice. Administration of botryosphaeran by gavage (doses: 7.5, 15, 30 mg/kg b.w./day) in a 30-day pretreatment protocol (young mice), or 15-day protocol (older mice), did not cause genotoxicity as assessed by the micronucleus test in peripheral blood (PB) and bone marrow cells (BMCs). Furthermore, there was no cytotoxic effect of this β-d-glucan in the treatments. A lower frequency of micronuclei was observed in BMCs from young and old mice that received botryosphaeran, indicating its antimutagenic effect. Botryosphaeran (30 mg/kg b.w./day) promoted 102.22% (young) and 103.45% (elderly) reductions in cyclophosphamide-induced damage in male mice. Botryosphaeran also exerted chemoprotective effects in LDLr−/− and wild-type (C57BL/6) mice. Botryosphaeran treatment for 15 days at a dose of 30 mg/kg b.w./day improved the lipidic profile (reductions of 53.8–84.3%), and decreased aortic lipid deposition (32.8%) in the LDLr−/− atherosclerotic mice. The results indicate botryosphaeran has relevant biologic effects, making it a promising candidate for the development of new therapeutic agents.

Protective effects of new Wenshen Shengjing Decoction on cyclosporine-induced impairment of testosterone synthesis and spermatogenic apoptosis.

The aim of the present study was to investigate the potential protective effects of new Wenshen Shengjing Decoction (new WSSJD; including Cornu Cervi Nippon Parvum, Panax ginseng, Cynomorium songaricum, Cistanche deserticola, Radix Astragali, Epimedium brevicornum and Angelica sinensis) on cyclosporine-induced impairment of testosterone synthesis and spermatogenic apoptosis in mice. A total of 90 adult male Kunming mice were divided into the following 6 groups: Control (no intervention), dimethylsulfoxide (DMSO; received only DMSO), cyclosporine A (CsA), clomifene citrate (CC; CsA + CC, 15 mg/kg/day), WSSJD (CsA + WSSJD, crude drug 12 g/kg/day) and new WSSJD (CsA + new WSSJD, crude drug 12 g/kg/day). All mice were treated for 30 days via oral gavage. The testes were subsequently fixed and stained with hematoxylin & eosin to assess the development of seminiferous epithelia. Immunohistochemical techniques were used to detect the expression of luteinizing hormone receptor (LHR) and P450 side chain cleavage (P450scc) in testicular Leydig cells. In addition, the apoptosis of spermatogenic cells in the testes was detected using a terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling assay, and flow cytometry was used to analyze the survival rate and early apoptosis of sperm in the epididymis. Compared with the CsA and CC groups, new WSSJD administration significantly increased levels of serum testosterone and the expressions of LHR and P450scc in testicular Leydig cells (P<0.05), while the apoptosis of spermatogenic cells in the seminiferous tubules and early apoptosis of mature sperm were significantly decreased (P<0.05). These results suggest that new WSSJD may ameliorate CsA-induced spermatogenic damage in male mice by enhancing testosterone synthesis and the secretion of testicular Leydig cells, and by reducing the apoptosis of spermatogenic cells.

The Protective Effect of Selenium on Chronic Zearalenone-Induced Reproductive System Damage in Male Mice.

This study aims to explore the protective effect of selenium (Se) on chronic zearalenone (ZEN)-induced reproductive system damage in male mice and the possible protective molecular mechanism against this. The chronic ZEN-induced injury mouse model was established with the continuous intragastric administration of 40 mg/kg body mass (B.M.) ZEN for 28 days. Then, interventions with different doses (0.1, 0.2, and 0.4 mg/kg B.M.) of Se were conducted on mice to analyse the changes in organ indexes of epididymis and testis, antioxidant capability of testis, serum level of testosterone, sperm concentration and motility parameters, and the expression levels of apoptosis-associated genes and blood testis barrier- (BTB) related genes. Our results showed that Se could greatly improve the ZEN-induced decrease of epididymis indexes and testis indexes. Results also showed that the decrease in sperm concentration, sperm normality rate, and sperm motility parameters, including percentage of motile sperm (motile), tropism percentage (progressive) and sperm average path velocity (VAP), caused by ZEN were elevated upon administration of the higher dose (0.4 mg/kg) and intermediate dose (0.2 mg/kg) of Se. Selenium also significantly reduced the content of malondialdehyde (MDA) but enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the testis tissue. Further research demonstrated that ZEN increased the level of mRNA expression of BCL2-associated X protein (Bax) and caspase 3 (Casp3), decreased the level of mRNA expression of B cell leukemia/lymphoma 2 (Bcl2), vimentin (Vim) and cadherin 2 (Cdh2), whereas the co-administration of Se reversed these gene expression levels. Our results indicated that high levels of Se could protect against reproductive system damage in male mice caused by ZEN and the mechanism might such be that Se improved mice antioxidant ability, inhibited reproductive cell apoptosis, and increased the decrease of BTB integrity-related genes caused by ZEN.

Proanthocyanidin protects against acute zearalenone-induced testicular oxidative damage in male mice.

Zearalenone (ZEN) exerts a major effect on human and animal health and has led to serious worldwide economic problems. In this study, we investigated whether proanthocyanidin (PC) can prevent ZEN-induced testicular oxidative damage in male mice and explored the underlying mechanism. Kunming mice were injected with ZEN (40mgkg-1) on the 11th day after intragastric administration of PC (75 or 150mg/kg) for 10days; the sperm quality of mice was then analysed statistically. Additionally, testicular morphology parameters related to oxidative damage, apoptosis and the expression of endoplasmic reticulum (ER) stress-related genes (GRP78, CHOP and XBP-1) were all measured. Results showed that ZEN exposure significantly reduced the sperm density, improved the sperm aberration rate, increased the MDA level and reduced SOD and GSH-Px activities. Meanwhile, ZEN was attributed to the downregulation of the expressions of the gene and protein of Bcl-2 and upregulation of the expressions of the gene and protein of Bax and caspase-3. ZEN exposure also upregulated the mRNA expression of GRP78, CHOP and XBP-1; however, PC pre-treatment reduced ZEN-induced oxidative damage and tended to maintain normal testicular morphology. Furthermore, PC pre-treatment substantially downregulated the expressions of the GRP78, CHOP and XBP-1 and upregulated the expression of the Bcl-2 gene. In conclusion, PC, due to its anti-oxidative ability, could ameliorate ZEN-induced testicular reproductive toxicity in male mice by decreasing ER stress and testicular cell apoptosis.

Antioxidant activity and hepatoprotective potential of Cedrelopsis grevei on cypermethrin induced oxidative stress and liver damage in male mice.

BackgroundThe liver is the most sensitive and main target organ of pesticide toxicity and damage, they play an essential role in metabolism and detoxification of pesticides. Due to these functions, hepatotoxicity continues to be among the main threats to public health, and they remain problems throughout the world. Therefore, the present study was designed to evaluate the antioxidant and hepatoprotective effects of Cedrelopsis grevei leaves against cypermethrin (Cyp) induced oxidative stress and liver damage in male mice.MethodsThe extracts were subjected to different analyses (phenolics, tannin, flavonoids, antioxidant activity and reducing power assays). For hepatoprotective evaluation, male mice were daily exposed to Cyp and/or C. grevei by gavages for 28 days. Hepatoprotective effects were demonstrated by significant alterations in serum liver dysfunction biomarker enzymes, liver lipid peroxidation and antioxidant enzymes.ResultsThe antioxidant activity of C. grevei methanolic extract was the highest with an IC50 < 225 μg/ml by DPPH assay. The high dose of methanolic extract (300 mg/kg. b.wt.) was effective to attenuate the perturbations in the tested enzymes. Histopathological examination in the liver tissue of those mice, demonstrated that a co-administration of methanolic extract (150 & 300 mg/kg/day) showed marked improvement in its histological structure in comparison to Cyp-treated group alone and represented by nil to moderate degree in inflammatory cells.ConclusionsIn view of the data of the present study, it can deduce that cypermethrin caused oxidative damage and liver dysfunction in male mice. C. grevei extract has protective effects on cypermethrin-induced lipid peroxidation, oxidative stress and liver damage. Results indicated that administration of C. grevei is useful, easy, and economical to protect humans against pesticide toxicity. The results presented here can be considered as the first information on the hepatoprotective and antioxidant properties of C. grevei extracts. In a future study, we will identify and investigate the components responsible for the hepatoprotective and antioxidant activities of C. grevei.

Curcumin improves liver damage in male mice exposed to nicotine

The color of turmeric (薑黃 jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice.Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied.The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p < 0.05). However, curcumin and curcumin plus nicotine administration substantially increased liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and nitric oxide levels in all groups compared with the nicotine group (p < 0.05).Curcumin demonstrated its protective effect against nicotine-induced liver toxicity.

Protective effect of hydroalcoholic extract of tribulus terrestris on Cisplatin induced renal tissue damage in male mice.

Background:According beneficial effects of Tribulus terrestris (TT) extract on tissue damage, the present study investigated the influence of hydroalcoholic extract of TT plant on cisplatin (CIS) (EBEWE Pharma, Unterach, Austria) induced renal tissue damage in male mice.Methods:Thirty mice were divided into five groups (n = 6). The first group (control) was treated with normal saline (0.9% NaCl) and experimental groups with CIS (E1), CIS + 100 mg/kg extract of TT (E2), CIS + 300 mg/kg extract of TT (E3), CIS + 500 mg/kg extract of TT (E4) intraperitoneally. The kidneys were removed after 4 days of injections, and histological evaluations were performed.Results:The data were analyzed using one-way analysis of variance followed by Tukey's post-hoc test, paired-sample t-test, Kruskal–Wallis and Mann–Whitney tests. In the CIS treated group, the whole kidney tissue showed an increased dilatation of Bowman's capsule, medullar congestion, and dilatation of collecting tubules and a decreased in the body weight and kidney weight. These parameters reached to the normal range after administration of fruit extracts of TT for 4 days.Conclusions:The results suggested that the oral administration of TT fruit extract at dose 100, 300 and 500 mg/kg body weight provided protection against the CIS induced toxicity in the mice.

5TNF-α and IL-1β neutralization ameliorates angiotensin II-induced cardiac damage in male mice.

Inflammation is a key event in hypertensive organ damage, and TNF-α and IL-1β are elevated in hypertension. In this study, we evaluated the effects of TNF-α and IL-1β elevation on hypertensive cardiac damage by treatment with a bifunctional inflammatory inhibitor, TNF receptor 2-fragment crystalization-IL-1 receptor antagonist (TFI), which can neutralize these 2 cytokines simultaneously. A mouse hypertension model of angiotensin II (Ang II) infusion (1500 ng/kg·min for 7 d) was induced in wild-type mice. TNF-α and IL-1β were inhibited by TFI administration (5 mg/kg, every other day), the effects of inhibition on cardiac damage were examined, and its mechanism on inflammatory infiltration was further studied in vivo and in vitro. Ang II infusion induced cardiac injury, including increased macrophage infiltration, expression of inflammatory cytokines (IL-12, IL-6, etc), and cardiac fibrosis, such as elevated α-smooth muscle actin, collagen I, and TGF-β expression. Importantly, the Ang II-induced cardiac injury was suppressed by TFI treatment. Moreover, TFI reduced the expression of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and monocyte chemotactic protein-1 expression in Ang II-treated hearts. Additionally, blockade of TNF-α and IL-1β by TFI reduced monocyte adherence to endothelia cell and macrophage migration. This study demonstrates that blocking TNF-α and IL-1β by TFI prevents cardiac damage in response to Ang II, and targeting these 2 cytokines simultaneously might be a novel tool to treat hypertensive heart injury.

Renoprotective effect of black tea against aflatoxin induced toxicity in mice

Tea is one of the most common beverages in the world. Leaves of Camellia sinensis (Black tea) possess antioxidant, renoprotective and antiapoptotic properties. The present study investigates the effect of black tea (Theaceae) infusion on aflatoxin induced renal damage in male mice. Aflatoxin B1 was orally administered at two doses of 750 and 1,500 mg/kg body weight, for 30 days. Then the black tea infusion was administered at a concentration of 2% in drinking water, simultaneously along with aflatoxin. Biochemical and histopathological analysis were done on 31st day of treatment. Aflatoxin treatment caused significant reduction (−17%) in body weight and corresponding increase in relative organ weight (52%). Aflatoxin at higher dose also caused significant increases in activities of alanine aminotransferase (81%), aspartate aminotransferase (55%), acid phosphatase (32%) and serum creatinine levels (58%) with concurrent decrease in alkaline phosphatase (−23%), succinate dehydrogenase (−44%) adenosine triphosphatase (−45%) activities and serum protein content (−19%). Histopathological changes showed that aflatoxin results in massive disorganization of both glomerular and tubular structures. However, black tea infusion significantly restores these damages at both doses. Thus the use of tea as dietary supplements therefore can be beneficial for the prevention of deteriorative effects of xenobiotic agents.

Hepatoprotective Activity of Flavonoids Purified and Ethanolic Extract from Iraqi Propolis Against Carbon tetrachloride-Induced Liver Damage In Male Mice

The present study aims to investigatethe antioxidant activity of flavonoids purified and methanolic extract from propolis on male mice compared to that caused by carbon tetrachloride as a hepatotoxic model by measuring the determination of catalase, glutathione peroxidase and superoxide dismutase change in liver damage. The results showed that the enzymes antioxidants (Glutothinone peroxidase (GPx) and Superoxide dismutase (SOD) had increased significantly (P <0.0l5) after it has been feeding male mice carbon tetrachloride, and that each of the flavonoids purified at a concentration (500 and 1000 mg / kg) and ethanolic extract at a concentration (500 mg / kg) has led to decreased Glutothinone peroxidase enzyme (GPx) activity significantly (P <0.05) compared to the control treatment after feeding them for 14 days. The ethanolic extract for propolis concentration of 1000 mg / kg and vitamin C concentration of 180 mg / kg has led to increased significantly (P <0.05) when compared with the treatment of control but a level significantly lower (P <0.05) compared with the treatment tetrachloride carbon.Either Superoxide dismutase (SOD) has led flavonoids pure and ethanolic extract for propolis ( 500 and 1000 mg / kg) to increase significantly the level (P <0.05) compared to treatment tetrachloride carbon, and vitamin C which led to a decline in the level of the enzyme significantly (P < 0.05) when feeding them for 14 days. Either enzyme catalase (CAT) has led flavonoids pure and ethanol extract of propolis ( 500 and 1000 mg / kg) to decrease significantly (P <0.05) compared to treatment tetrachloride carbon and control group as well as when feeding with vitamin C and ethanol extract alone at a concentration (1000 mg / kg) led to a significant decrease of the level (P <0.05). The study concluded that flavonoids pure and ethanolic extract of Iraqi propolis has led to a reduction of the inhibitory effect as well as for damage to the work of the liver and there by protect members from free radicals and inhibit the liberation of these ROS.

Chemopreventive Role of Euphorbia neriifolia (Linn) and its Isolated Flavonoid Against N-Nitrosodiethylamine-induced Renal Histopathological Damage in Male Mice.

Aims:This study is an attempt to evaluate the tissue protective efficacy of isolated flavonoid and hydro-ethanolic extract of Euphorbia neriifolia (HEEN) leaves against N-nitrosodiethylamine (DENA) induced renal carcinoma.Materials and Methods:Carcinogenicity was induced in Albino mice by oral administration of DENA (50 mg/kg body weight). The HEEN (150 and 400 mg/kg body weight), Butylated hydroxyanisole (BHA; 0.5 and 1%), and Euphorbia neriifolia flavonoid (ENF; 50 mg/kg body weight) were evaluated for their possible tissue carcinogenesis protective potential.Results:DENA treated animals showed alterations in normal renal histo-architecture, which comprised of necrosis (N) and vacuolization of the cells. On the other hand, the mice treated with Euphorbia neriifolia lower (ENL) and higher (ENH) dose and ENF before intoxicated with DENA showed that the renal cells were normal (Day 31). Whereas, BHA higher (BHAH) and lower (BHAL) dose failed to diminish the abnormalities caused by DENA.Conclusions:The findings of the present study Suggested that ENH and ENF showed highest renal-protective activity among all the pretreatments. The results could also be expressed in the order of ENH > ENF > ENL > BHAH > BHAL.

Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice

Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles.