Impacts of n-acetyl cysteine on gibberellic acid-induced testicular dysfunction through regulation of inflammatory cytokines, steroid and antioxidant activity.

In agriculture, gibberellic acid (GA3) is commonly used with extreme dangers for public health. The current research evaluates the improving effects of n-acetyl cysteine (NAC, 150 mg/kg bw) co-administered with GA3 (55 mg/kg bw) mediated testicular injury. Twenty-four male albino rats were split into 4 groups: Negative control (CNT), NAC group, positive GA3 group and protective group, co-administered NAC plus GA3. On day 21, rats were anesthetised then euthanised by decapitation. Blood samples were collected; testicular samples were taken for semen analysis, serum chemistry, RNA extraction, histological and antioxidants markers examination. Our results revealed a significant decline p < .05 of catalase level and total antioxidant capacity. There was a substantial rise of MDA concentration in GA3-treated rats along with a considerable decrease of the antioxidant markers (SOD, GSH) and serum male reproductive hormones. In GA3-treated rats, an overexpression of the inflammatory cytokines (TNF-α, IL-1ß) and anti-inflammatory cytokine IL-10 with boost mRNA expression of nuclear factor-kappa (NFk B) were confirmed. There was downregulation of steroidogenesis genes and decrease in sperm quality and concentration with an increase in sperm abnormalities, all were reported in GA3-treated rats. NAC treatment significantly increased the antioxidant state, testicular function beside structural germ cell and seminiferous tubules histology accompanied by upsurge of steroidogenic mRNA expressions (P450scc and 3ß-HSD) and downregulated the pro-inflammatory cytokines mRNA expression (TNF-α, IL-1ß). These results confirm the antioxidant capability of NAC and afford robust evidence about the ameliorative effect of the NAC to attenuate the testicular injury induced by GA3 through modulation of the antioxidant defence system, steroidogenic and pro-inflammatory cytokines mRNA expression.

Ameliorative impacts of chrysin against gibberellic acid-induced liver and kidney damage through the regulation of antioxidants, oxidative stress, inflammatory cytokines, and apoptosis biomarkers.

Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50 mg/kg/BW orally daily for 4 weeks; the GA3 group received 55 mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-administration of chrysin significantly protected the hepatorenal tissue against the deleterious effects of GA3. Chrysin restored the hepatorenal functions and their antioxidant ability to normal levels. Moreover, chrysin modulated the hepatorenal toxic effects of GA3 at the molecular level via the upregulation of the antiapoptotic genes, interleukin-10 (IL-10), hemoxygenase-1, and nuclear factor erythroid 2-related factor 2 expressions; the downregulation of the kidney injury molecule-1 and caspase-3 mRNA expressions; and a decrease in IL-1ß and tumor necrosis factor-α secretions. Additionally, the pre-administration of chrysin effectively attenuated the GA3-induced hepatorenal histopathological changes by regulating the immunoexpression of cytochrome P450 2E1 (CYP2E1) and pregnane X receptor, resulting in normal values at the cellular level. In conclusion, chrysin attenuated GA3-induced oxidative hepatorenal injury by inhibiting free-radical production and cytokine expression as well as by modulating the antioxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.

Impacts of n-acetyl cysteine on gibberellic acid-induced hepatorenal dysfunction through modulation of pro-inflammatory cytokines, antifibrotic and antioxidant activity.

The extensive usage of gibberellic acid (GA3) in agriculture and plant growth is generally associated with enormous human and public health hazards. The present research assesses the impact of n-acetyl cysteine (NAC) on the hepatorenal injury persuaded by GA3 for this purpose, After two weeks of adaptation twenty-four rats allocated into four groups (6 rats/group) as follows: control group, supplied with saline only; n-acetyl cysteine (NAC) group, provided with 150 mg/kg/bw by stomach tube (orally) dissolved in saline; Positive GA3 group, received GA3 (55 mg/kg/bw) orally; Protective group received NAC (150 mg/kg/bw) and GA3 (55 mg/kg/bw) as in NAC and GA3 groups. Rats received their treatments for consecutive 3 weeks. On day 22, rats were anesthetized, then euthanized. Blood and tissue samples were obtained for biochemical, antioxidants markers analysis, gene expression, and histopathological examination. Our results revealed significant changes in serum AST, ALT, urea, uric acid, total protein, and albumin levels with a substantial rise of MDA and NO concentration in GA3 treated rats along with a considerable decrease of the GSH and overexpression of the inflammatory hepatic and renal cytokines (IL-10, TNF-α, NOS) and fibrotic gene expression TGF-ß1, and α-SMA, with boost expression of nuclear factor-kappa (NFk B). NAC co-administered with GA3 significantly normalized the kidney and liver function and the antioxidant state, besides normal histological structure of both liver and kidney tissue and downregulated expression of the pro-inflammatory cytokines as well as, fibrogenic gene expression. PRACTICAL APPLICATIONS: The current study confirmed that GA3 induced hepto-renal dysfunction that was ameliorated by NAC administration. Moreover, our findings confirmed the antioxidant capability of n-acetyl cysteine and afford robust evidence about the ameliorative effect of the n-acetyl cysteine to attenuate the hepatorenal injury induced by gibberellic acid through modulation of the antioxidant defense system fibrogenic, and pro-inflammatory cytokines expression.

The modulatory impacts of Glycyrrhiza glabra extract against methotrexate-induced testicular dysfunction and oxidative stress.

Glycyrrhiza glabra root (licorice) is a widely used herb for its beneficial effects on health. This study explored the protective effects of licorice extract against oxidative stress and testicular dysfunction caused by methotrexate (MTX). Mice were allocated into (i) negative control group that received saline; (ii) licorice extract group, orally administered with 200 mg/kg body weight (bw) licorice extract for 12 days; (iii) positive MTX-intoxicated group, injected with a single intraperitoneal dose of MTX (20 mg/kg bw) on day 7; and (iv) a protective group that received licorice extract for 12 days and then MTX on day 7 as in groups 2 and 3. Total proteins, albumin, globulins, malondialdehyde, glutathione peroxidase, reduced glutathione, IL-1, and IL-6 were measured in blood and testis samples collected from all groups. Testicular oxidative stress, serum reproductive hormones, and spermogram were examined. The expression of steroidogenesis-associated genes (translocator protein; and P450scc) was examined by quantitative real-time PCR. Bcl-2-associated X protein and cyclogenase-2 genes were examined by immunohistochemical analysis. The bioactive contents of licorice extract were confirmed by gas chromatography-mass spectrometry analysis. Pretreatment with licorice extract ameliorated the toxic effects of MTX on total proteins, albumin, and globulins and oxidative stress biomarkers and reversed the effect of MTX on examined serum and tissue antioxidants. Besides, MTX down-regulated mRNA expression of translocator protein and P450scc genes. Licorice extract averted the decrease in serum testosterone and the increase in IL-1ß and IL-6 levels induced by MTX. Moreover, MTX increased sperm abnormalities and percentage of dead sperms and reduced sperm motility. These changes were absent in the licorice preadministered group. Licorice prevented the increase in immunoreactivity of testis for Bcl-2-associated X protein and cyclogenase-2 that were overexpressed in MTX-injected mice. Licorice extracts positively regulated the expression of steroidogenesis genes suppressed by MTX, increased antioxidant enzymes (glutathione peroxidase, reduced glutathione, and catalase) and reduced biomarker of oxidative stress (testicular malondialdehyde) and inflammatory cytokines (IL-1 and -6). Moreover, reduction in testicular tissue immunoreactivity to Bcl-2-associated X protein and cyclogenase-2. In conclusion, licorice extract mitigated the toxic effects of MTX-induced testicular dysfunction at biochemical, molecular, and cellular levels.

Molecular and Histopathological Study on the Ameliorative Impacts of Petroselinum Crispum and Apium Graveolens against Experimental Hyperuricemia.

Hyperuricemia is an abnormal metabolic condition characterized by an increase in uric acid levels in the blood. It is the cause of gout, manifested by inflammatory arthritis, pain and disability. This study examined the possible ameliorative impacts of parsley (PAR) and celery (CEL) as hypouricemic agents at biochemical, molecular and cellular levels. PAR and CEL alone or in combination were orally administered to hyperuricemic (HU) mice and control mice for 10 consecutive days. Serum levels of uric acid and blood urea nitrogen (BUN), xanthine oxidase activity, antioxidants, inflammatory (IL-1ß and TNF-α) and anti-inflammatory cytokines (IL-10) were measured. mRNA expression of urate transporters and uric acid excretion genes in renal tissues were examined using qRT-PCR (quantitative real time PCR). Normal histology and immunoreactivity of transforming growth factor-beta 1 (TGF-ß1) in kidneys was examined. Administration of PAR and CEL significantly reduced serum BUN and uric acids in HU mice, ameliorated changes in malondialdehyde, catalase, and reduced glutathione, glutathione peroxidase (GPX), IL-1ß, TNF-α and IL-10 in hyperuricemic mice. Both effectively normalized the alterations in mURAT-1, mGLUT-9, mOAT-1 and mOAT-3 expression, as well as changes in TGF-ß1 immunoreactivity. Interestingly, combined administration of PAR and CEL mitigated all examined measurements synergistically, and improved renal dysfunction in the hyperuricemic mice. The study concluded that PAR and CEL can potentially reduce damaging cellular, molecular and biochemical effects of hyperuricemia both individually and in combination.

Protective Impacts of Moringa oleifera Leaf Extract against Methotrexate-Induced Oxidative Stress and Apoptosis on Mouse Spleen.

OBJECTIVE: The current study was aimed to examine the possible ameliorative impacts of MO leaf extract (MOLE) against MTX-induced alterations on oxidative stress of mouse spleen and explore the possible molecular mechanism that controls such impacts. METHODS: Adult male mice were allocated into 4 groups: control, Moringa oleifera leaf extract (MOLE), MTX, and MOLE plus MTX. Mice received MOLE orally for a week before MTX injection and continued for 12 days. Serum and spleen were sampled for biochemical and quantitative gene expressions. RESULTS: As compared with the MTX-injected group, MOLE effectively reduced the changes in total proteins, spleen MDA, SOD and catalase activities, and changes in serum antioxidants levels. Moreover, there is downregulation of antioxidant genes (SOD and catalase) and antiapoptotic genes (XIAP and Bcl-xl) along with upregulation in Bax and caspase-3 mRNA (apoptotic genes) in the MTX-injected group. MTX induced changes in IL-1ß, IL-6, TNF-α, and IL-10 expression. MOLE restored and ameliorated the changes induced in biochemical, antioxidants, apoptosis, and apoptosis associated genes that were induced by MTX intoxication. CONCLUSION: Current findings indicated that pretreatment with MOLE to MTX-intoxicated mice showed the potential usage of MO for oxidative stress and apoptosis treatment.

The ameliorative impacts of Moringa oleifera leaf extract against oxidative stress and methotrexate-induced hepato-renal dysfunction.

Moringa Oleifera (MO) is a herbal plant native to South Asia known for its anti-oxidative and anti-inflammatory properties. This study explored the protective effects of MO leaf extract (MOLE) against oxidative stress and hepatic and renal injuries caused by methotrexate (MTX) therapy. Mice received a single intraperitoneal injection of 20 mg/kg body weight MTX to induce hepatic and kidney injuries. They then received 300 mg/kg body weight of MOLE orally for seven days, followed by MTX on day 7 then five more days of MOLE (12 days total). Blood, liver and kidney samples were collected from all groups and the following biochemical parameters were tested: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase, superoxide dismutase (SOD), malondialdehyde (MDA) and total proteins. Quantitative real time PCR (qRT-PCR) was used to examine Nrf2, HO-1, BAX, TIMP, XIAP, and NFkB, which are associated with apoptosis, anti-apoptosis and oxidative stress. Capase-9 and Bcl2 genes underwent immunohistochemical analysis. Pretreatment with MOLE reduced the effect of MTX on ALT, AST and total proteins, and reversed its effect on serum and tissue antioxidants. Nrf2/HO-1, apoptotic and anti-apoptotic gene expression was regulated, and Bax and TIMP were reduced; XIAP expression was increased in both the liver and kidney samples, and immunoreactivity of caspase-9 and Bcl2 was restored in the MOLE-administered experimental group. Overall, the study concluded that MOLE can inhibit the effects of hepato-renal injuries caused by MTX by regulating oxidative stress, apoptosis and anti-apoptotic genes at biochemical, molecular and cellular levels.

Mast cells and pro-inflammatory cytokines roles in assessment of grape seeds extract anti-inflammatory activity in rat model of carrageenan-induced paw edema.

OBJECTIVES: Reactive oxygen species (ROS)-produced oxidative disorders were involved at the pathophysiology of many inflammatory processes via the generation of pro-inflammatory cytokines and antioxidant defense system suppression. Although herbal antioxidants as mono-therapy relief many inflammatory diseases including, autoimmunity rheumatoid arthritis, but as combination therapy with other proven anti-inflammatory drugs in order to decreasing their toxic impacts has not yet been studied clearly, especially against chemical substances that's induced local inflammation with characteristic edema. MATERIALS AND METHODS: Grape seeds extract (GSE) at a concentration of 40 mg/kg B. wt alone or in combination with indomethacin (Indo.) at a dose of 5 mg/Kg B. wt orally given for 10 days prior (gps VI, VII, VIII) or as a single dose after edema induction (gps IX, X, XI) in rat's left hind paw by sub-planter single injection of 0.1 carrageenan: saline solution (1%) (gp. V) to assess the prophylactic and therapeutic anti-inflammatory activities of both through the estimation of selective inflammatory mediators and oxidative damage-related biomarkers as well as tissue mast cell scoring. Furthermore, both substances were given alone (gps II, III, IV) for their blood, liver and kidney safety evaluation comparing with negative control rats (gp. I) which kept without medication. RESULTS: A marked reduction on the inflammatory mediators, edema volume and oxidative byproducts in edema bearing rats' prophylactic and treated with grape seeds extract and indomethacin was observed. Indomethacin found to induce some toxicological impacts which minimized when administered together with GSE. CONCLUSION: GSE is a safe antioxidant agent with anti-inflammatory property.

The ameliorative potential of ethanolic extract of propolis on hematotoxicity and structural neuronal damage in hyperthermia-exposed rats.

OBJECTIVES: Hyperthermia is one of the most common environmental stressors that affect multi-biological systems in the body including the central nervous system as well as the hematopoietic organs. The objective of the present study was to investigate the protective role of ethanolic extract of propolis (EEP) on some selective stress markers, hematological, biochemical, and histopathological changes in rats subjected to hyperthermia (40 °C/12 hr). MATERIALS AND METHODS: The experimental groups (10 rats each) were classified as follows; Group A; control, (C), was kept at a controlled room temperature (25±5 °C). Group B; ethanolic extract of propolis, (EEP), was fed a basal diet supplemented with 3 g EEP/kg diet for 10 days. Group C; heat stress, (HS), was fed a basal diet for 10 days, and then exposed to high temperature (40±1 °C) for 12 hr. Group D; co-exposed, (EEP+HS) was fed a basal diet supplemented with 3 g EEP/kg diet for 10 days, and then subjected to high temperature (40±1 °C) for 12 hr. At the end of the experimental period, animals were decapitated; blood and tissue samples (brain and spleen) were collected for hematological, biochemical, and histopathological examination. RESULTS: EEP at a dose of 3 g/kg diet has a potent protective effect against hematotoxicity and brain damage as well as oxidative stress induced by heat stress in rats. CONCLUSION: The present study indicates that pre-treatment with EEP protects from hematotoxicity and neurological damage induced by high environmental temperature.