Ameliorative impacts of sinapic acid against mercuric chloride-induced renal toxicity: role of antioxidants and inflammatory cytokines.

Because of their beneficial properties, natural products, especially medicinal plants, are becoming increasingly popular worldwide and play a significant role in research. This study was aimed to evaluate the nephroprotective effect of sinapic acid against mercuric chloride-induced renal toxicity in mice. The mice were allocated to four groups named a normal group (G1), model group (G2; received HgCl2, 1 mg/kg bw), treatments groups (G3 and G4: received 50 and 100 mg/kg bw of sinapic acid together with HgCl2). Mice received HgCl2 remarkably showed alteration in all examined biochemical biomarkers (urea, creatinine, and bilirubin), and induced alteration in blood cell picture and anemia. HgCl2 intoxication decreased both systemic and renal antioxidant activity and induced over all oxidative stress as indicated by alteration in inflammation and oxidative stress associated markers. HgCl2 affected renal histology with leukocytic and inflammatory cell infiltration, fibrosis and tubular necrosis. Administration of sinapic acid (50 and 100 mg/kg bw) markedly restored the HgCl2-induced oxidative stress (serum and renal: MDA, GSH, CAT, SOD, and T-AOC), proinflammatory cytokines (serum and renal: TNF-α, IL-6, IL-1ß, and PGE2) and restored the changes on biochemical markers, and hematological parameters (hemoglobin, erythrocytes, platelets, and leukocytes). Taken together, the results of the present study disclose that sinapic acid has the potential to attenuate HgCl2-induced renal toxicity and may be an ideal choice against mercury poisoning.

Anti-inflammatory potential of stevia residue extract against uric acid-associated renal injury in mice.

Abnormal uric acid level result in the development of hyperuricemia and hallmark of various diseases, including renal injury, gout, cardiovascular disorders, and non-alcoholic fatty liver. This study was designed to explore the anti-inflammatory potential of stevia residue extract (STR) against hyperuricemia-associated renal injury in mice. The results revealed that STR at dosages of 150 and 300 mg/kg bw and allopurinol markedly modulated serum uric acid, blood urea nitrogen, and creatinine in hyperuricemic mice. Serum and renal cytokine levels (IL-18, IL-6, IL-1Β, and TNF-α) were also restored by STR treatments. Furthermore, mRNA and immunohistochemistry (IHC) analysis revealed that STR ameliorates UA (uric acid)-associated renal inflammation, fibrosis, and EMT (epithelial-mesenchymal transition) via MMPS (matrix metalloproteinases), inhibiting NF-κB/NLRP3 activation by the AMPK/SIRT1 pathway and modulating the JAK2-STAT3 and Nrf2 signaling pathways. In summary, the present study provided experimental evidence that STR is an ideal candidate for the treatment of hyperuricemia-mediated renal inflammation. PRACTICAL APPLICATIONS: The higher uric acid results in hyperuricemia and gout. The available options for the treatment of hyperuricemia and gout are the use of allopurinol, and colchicine drugs, etc. These drugs possess several undesirable side effect. The polyphenolic compounds are abundantly present in plants, for example, stevia residue extract (STR) exert a positive effect on human health. From this study results, we can recommend that polyphenolic compounds enrich STR could be applied to develop treatment options for the treatment of hyperuricemia and gout.

An In Vitro and In Silico Perspective Study of Seed Priming with Zinc on the Phytotoxicity and Accumulation Pattern of Arsenic in Rice Seedlings.

Arsenic (As) contamination of the rice agro-ecosystem is a major concern for rice farmers of South East Asia as it imposes a serious threat to human and animal life; thus, there is an unrelenting need to explore the ways by which arsenic stress mitigation could be achieved. In the present investigation, we explore the effect of zinc (Zn2+) supplementation using the seed priming technique for the mitigation of As-induced stress responses in developing rice seedlings. In addition to the physiological and biochemical attributes, we also studied the interactive effect of Zn2+ in regulating As-induced changes by targeting antioxidant enzymes using a computational approach. Our findings suggest that Zn2+ and As can effectively modulate redox homeostasis by limiting ROS production and thereby confer protection against oxidative stress. The results also show that As had a significant impact on seedling growth, which was restored by Zn2+ and also minimized the As uptake. A remarkable outcome of the present investigation is that the varietal difference was significant in determining the efficacy of the Zn2+ priming. Further, based on the findings of computational studies, we observed differences in the surface overlap of the antioxidant target enzymes of rice, indicating that the Zn2+ might have foiled the interaction of As with the enzymes. This is undoubtedly a fascinating approach that interprets the mode of action of the antioxidative enzymes under the metal/metalloid-tempted stress condition in rice by pointing at designated targets. The results of the current investigation are rationally significant and may be the pioneering beginning of an exciting and useful method of integrating physiological and biochemical analysis together with a computational modelling approach for evaluating the stress modulating effects of Zn2+ seed priming on As-induced responses in developing rice seedlings.

Incredible affinity of Kattosh with PPAR-γ receptors attenuates STZ-induced pancreas and kidney lesions evidenced in chemicobiological interactions.

Since ancient times, plants have been used as green bioresources to ensure a healthier life by recovering from different diseases. Kattosh (Lasia spinosa L. Thwaites) is a local plant with various traditional uses, especially for arthritis, constipation and coughs. This research investigated the effect of Kattosh stem extract (LSES) on streptozotocin-induced damage to the pancreas, kidney, and liver using in vitro, in vivo and in silico methods. In vitro phytochemical, antioxidative and anti-inflammatory effects of LSES were accomplished by established methods followed by antidiabetic actions in in vivo randomized controlled intervention in STZ-induced animal models for four weeks. In an in silico study, LSES phytocompounds interacted with antidiabetic receptors of peroxisome proliferator-activated receptor-gamma (PPAR, PDB ID: 3G9E), AMP-activated protein kinase (AMPK, PDB ID: 4CFH) and α-amylase enzyme (PDB ID: 1PPI) to verify the in vivo results. In addition, LSES showed promising in vitro antioxidative and anti-inflammatory effects. In contrast, it showed a decrease in weekly blood glucose level, normalized lipid profile, ameliorated liver and cardiac markers, managed serum AST and ALT levels, and increased glucose tolerance ability in the animal model study. Restoration of pancreatic and kidney damage was reflected by improving histopathological images. In ligand-receptor interaction, ethyl α-d-glucopyranoside of Kattosh showed the highest affinity for the α-amylase enzyme, PPAR, and AMPK receptors. Results demonstrate that the affinity of Kattosh phytocompounds potentially attenuates pancreatic and kidney lesions and could be approached as an alternative antidiabetic source with further clarification.

Protective potential of royal jelly against hydroxyurea -induced hepatic injury in rats via antioxidant, anti-inflammatory, and anti-apoptosis properties.

Hydroxyurea (HDU) is a widely used medication for various malignancies, thalassemia, and sickle cell anemia with reported side effects. The current study investigated HDU- induced hepatic injury and the protective potential of the royal jelly (RJ) against this hepatotoxic effect in the light of hepatic oxidative/ antioxidative status, pro-inflammatory cytokine, apoptosis signaling pathway, and histopathology. Sixty albino rats were used (n = 10/group) for 60 days: control, RJ (100 mg/kg body weight, orally), HDU (225 mg/kg body weight, orally), 2HDU (450 mg/kg body weight, orally), and HDU + RJ groups. HDU-treated rats showed significant elevation of liver function tests as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, as well as malondialdehyde and nitric oxide (oxidative biomarkers) and significant decreased hepatic antioxidant molecules (reduced glutathione, superoxide dismutase, and glutathione peroxidase), compared to a control group, that more pronounced in the high dose of HDU. In addition, HDU induced significant upregulation of TNF-α and the Caspase-3 apoptotic pathway. Moreover, the liver of HDU treated groups showed various hepatic lesions from mild to severe necrotic changes related to the HDU dose. However, administration of RJ with HDU improved liver function tests, liver histology, and hepatic oxidative/antioxidative status concerning HDU groups. Furthermore, oral RJ administration with HDU significantly lessens the immune-expression area % of TNF-α and Caspase-3. Thus, the royal jelly has antioxidant, anti-inflammatory, and anti-apoptotic properties against HDU- induced hepatic injury and could be, therefore, used as adjuvant therapy in patients with long-term HDU medication.

Beneficial impact of dietary methyl methionine sulfonium chloride and/or L-carnitine supplementation on growth performance, feed efficiency, and serum biochemical parameters in broiler chicken: role of IGF-1 and MSTN genes.

The purpose of this study was to examine the effect of dietary supplementation with methyl methionine sulfonium chloride (MMSC), and L-carnitine (L-CAR) alone or in combination on the growth performance of broilers through their impact on the expression of IGF-1 and MSTN genes associated with growth in broilers. One-day-old female Ross 308 broiler chicks were allocated into four groups, each of which received a broiler starter diet and water daily ad libitum. The control group (group 1) was given drinking water without any additives. Group 2 received 0.25 g L-carnitine per liter of drinking water, group 3 received 0.25 g MMSC per liter of drinking water, and group 4 received 0.25 g of both L-carnitine and MMSC per liter of drinking water. Birds were given a starter diet to 21 days after which they received a broiler grower diet to 35 days when the experiment ended. There were five replicate groups of 12 birds per treatment. Body weights and feed intake were recorded weekly. Compared to the control group of birds, supplementation with MMSC either alone or in combination with L-carnitine resulted in an increase in growth rate or feed utilization efficiency; L-carnitine by itself had no effect. MMSC supplementation, again either alone or in combination with L-carnitine, increased jejunal and ileal villi height, increased serum total proteins and globulins, downregulated myostatin (MSTN) mRNA, and upregulated insulin growth factor-1 (IGF-1) mRNA expression. Supplementation with L-carnitine alone showed none of these effects. We conclude that MMSC supplementation improved growth performance through the upregulation of IGF-1 mRNA expression and downregulation of MSTN mRNA expression.

Use of Zinc Oxide Nanoparticles as Anticoccidial Agents in Broiler Chickens along with Its Impact on Growth Performance, Antioxidant Status and Hematobiochemical Profile.

The impact of zinc oxide nanoparticles (ZnO-NPs) on the pathogenesis of coccidiosis in broiler chickens was tested. A total of 160 1-day-old broiler chicks (Ross 308) were randomly allocated into 4 groups (n = 40). Group 1: unchallenged, unmedicated; Group 2: challenged, unmedicated; Group 3: challenged, supplemented with diclazuril (1 ppm); Group 4: challenged, supplemented with ZnO-NPs (20 ppm). Mixed Eimeria species (E. maxima, E. acervulina, E. mivati, and E. tenella) of a commercial coccidial vaccine (FORTEGRA®) were used to perform the coccidial challenge by 15× of its vaccinal dose on the 14th day of age. Diclazuril and ZnO-NPs supplementation in Group 3 and 4, respectively, reduced the mortality rate due to coccidial challenge to 5.8% compared to 11.9% in Group 2. The growth performance was improved by ZnO-NPs in coccidiosis-infected group (p ≤ 0.05) compared to Group 2 and was comparable to that of Group 3 (p ≥ 0.05). The average oocyst count was lower in Groups 3 and 4 (7.8 × 103 and 14.3 × 103, respectively) than in Group 2 (67 × 103 oocysts). Group 3 had a decreased gross lesion score in duodenum and caecum (p ≤ 0.05) as well as jujenum and ileum (p ≥ 0.05) compared to Group 2; while the average lesion scores of all intestinal parts in Group 4 were significantly decreased (p ≤ 0.05). However, diclazuril was superior to ZnO-NPs in reducing caecal lesion score (p ≤ 0.05). Plasma carotenoids levels were increased by diclazuril (p ≥ 0.05) and ZnO-NPs (p ≤ 0.05) supplementation compared to Group 2. Oxidative stress appeared on the fourth week post-challenge (pc) in Group 2 (p ≤ 0.05) compared to Group 1, while the dietary supplementation with either diclazuril or ZnO-NPs numerically decreased Malondialdhyde (p ≥ 0.05) and statistically increased antioxidant activity (p ≤ 0.05). Both medications significantly improved the PCV%, Hb% and RBCs count on the 6th-day and 4th-week pc (p ≤ 0.05) compared to Group 2, though this improvement was higher significantly in Group 4 than Group 3 on the 6th day pc (p ≤ 0.05). Neither coccidial challenge nor medications had an impact on the total WBCs count as well as organ index, except Bursa of fabricious index that significantly improved by ZnO-NPs on the 4th-week pc compared to Group 2. Coccidial challenge reduced total protein and globulin levels and increased the serum alanine aminotransferase, serum cholesterol, and low-density lipoprotein levels (p ≤ 0.05) compared to Group 1, while those of both medicated groups (Group 3 and 4) were comparable to Group 1 (p ≥ 0.05). In conclusion, ZnO-NPs were found to be as effective as diclazuril against coccidiosis. However, further research is needed to fully comprehend its anticoccidial mechanisms.

Impact of Thymus vulgaris extract on sodium nitrite-induced alteration of renal redox and oxidative stress: Biochemical, molecular, and immunohistochemical study.

Thyme (Thymus vulgaris) is an herbal plant with pleiotropic medicinal properties. In this study, we examined the possible protective effect of an ethanolic extract of thyme leaves against the renal oxidative stress induced by sodium nitrite (NaNO2 ). Male Swiss mice received either saline or thyme extract for 15 days (0.5 g/kg body weight, orally). NaNO2 (60 mg/kg) was injected intraperitoneally at Day 14. The protective group received the thyme extract for 15 days and NaNO2 on Day 14. Blood and kidney samples were taken from all groups to measure serum urea, blood urea nitrogen (BUN), creatinine, serum, tissue antioxidant activity, and the inflammatory cytokines IL-1ß and IL-6. Quantitative real-time PCR (qRT-PCR) was used to examine the expression of kidney injury marker-1 (Kim-1), TNF-α, nuclear factor erythroid-2 related factor 2 (Nrf2), and hemoxygenase-1 (HO-1), all of which are associated with kidney redox and oxidative stress. Pretreatment with thyme extract reduced the effects of NaNO2 on urea, BUN, and creatinine, and reversed its effect on tissue and serum antioxidants. NaNO2 -induced nephritis as demonstrated by the upregulation in mRNA expression of Kim-1 and TNF-α, which was, however, recovered and protected by pretreatment with thyme extract. Expression of Nrf2 and HO-1 was upregulated by treatment with thyme extract and downregulated by NaNO2 intoxication. NaNO2 -induced congestion in glomeruli and dilatation of the renal tubules, conditions that were restored in the group pretreated with thyme extract. NaNO2 upregulated Bax immunoreactivity and caused apoptosis in renal structures. Thus, thyme extract is effective in managing the renal toxicity associated with oxidative stress and renal redox. PRACTICAL APPLICATIONS: The results from this study have shown that use of thyme extract may promote better health due to its high antioxidant activity. For instance, it could be ingested to alleviate the symptoms of renal inflammation and oxidative stress associated with nitrite toxicity. Thyme extract regulated renal redox, oxidative stress, antioxidant levels, and inflammation-associated genes at the molecular, biochemical, and cellular immunohistochemical levels.

Growth performance, economic efficiency, meat quality, and gene expression in two broiler breeds fed different levels of tomato pomace.

Male broiler chicks (135 Indian River chicks (IR) and 135 Cobb chicks; n = 270) were weighed, wing banded, and distributed randomly into three iso-energetic and iso-nitrogenous diet groups for each breed (triplicate design, 45 bird/group, 15 bird/replicate). The chicks were fed the diets with levels of 0, 4, or 6% sun-dried tomato pomace (SDTP), respectively, for 42 consecutive days to determine the effect of consuming different levels of SDTP on growth performance, economic efficiency, meat quality, and gene expression in IR and Cobb broiler chickens. The inclusion of up to 6% SDTP in the diet of IR or Cobb chickens had no negative impact on growth performance parameters. Chickens from both the IR and Cobb breeds fed a diet containing 4% or 6% SDTP consumed more feed than those fed a diet containing 0% SDTP. Concomitantly, the groups fed a 6% SDTP diet of IR breed incurred a significantly higher feed cost, total variable cost (TVC), and total cost (TC). The inclusion of up to 6% SDTP in the feed of both breeds resulted in a non-significant increase in return parameters. The ultimate pH decreased as the SDTP concentration increased, with no significant differences in water holding capacity (WHC) or drip loss (48 h). No alteration in the mRNA expression of hepatic growth hormone receptor gene (GHR) or insulin like growth factor-1 (IGF-1) was found among the treatments for either the IR or Cobb breeds. Thus, up to 6% SDTP can be added to the diet of IR and Cobb broiler chickens without any adverse effects on the examined parameters.

Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role.

Boldenone Undecylenate (BLD) is a synthetic derivative of testosterone and a widely used anabolic androgenic steroid. The health risk of BLD use as a pharmaceutical or dietary supplement is still underestimated and under-reported. Vitamin C (VC) has been recognized as an antioxidant with prominent hepatorenal protective effects. This study investigated the possible preventive activity of VC against BLD-induced hepatorenal damage. Forty adult male Wistar rats were classified into five groups: control, vehicle control, VC (orally given 120 mg/kg b. wt./day), BLD (intramuscularly injected 5 mg/kg b. wt./week), and BLD + VC-treated groups. The experiment continued for eight weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Serum contents of total protein (TP), albumin (ALB), globulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C) were also assayed. Urea, creatinine, and uric acid levels were determined together with sodium and potassium electrolytes measuring. Moreover, oxidative stress indicators including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GSR) as well as malondialdehyde (MDA) levels were measured in both hepatic and renal tissues. Corresponding histological examination of renal and hepatic tissues was conducted. Besides, immunohistochemical evaluations for androgen receptors protein (AR) and heat shock protein 90 (Hsp 90) expressions were performed. BLD caused significant rises in serum ALT, AST, TP, ALB, TC, TG, LDL-C, VLDL-C, urea, creatinine, uric acid, potassium, and MDA levels. Further, BLD-injected rats showed significant declines in the serum levels of HDL-C, sodium, GSH, GPx, GST, and GSR. Besides, distinct histopathological perturbations were detected in renal and hepatic tissues of BLD-injected rats. AR and Hsp 90 immunoexpression were increased in hepatic and renal tissues. In contrast, VC significantly reversed the BLD-induced hepatorenal damage in co-treated rats but not ameliorated AR protein overexpression. VC could be an efficient preventive supplement for mitigating BLD-induced hepatorenal damage, possibly via controlling oxidative stress events.

Grape seed extract ameliorated Ehrlich solid tumor-induced hepatic tissue and DNA damage with reduction of PCNA and P53 protein expression in mice.

This study evaluated the ameliorative potential of grape seed extract (GSE) against Ehrlich solid tumor (EST)-induced hepatic tissue alterations in mice. The control group was infused with physiological saline. The second group received GSE (50 mg/kg day by day orally) for 2 weeks. The third group was subcutaneously injected with 2.5 million of EST cells. The fourth group was injected with EST cells and treated with GSE extract simultaneously. The fifth group was injected with EST cells and kept for 2 weeks until the appearance of a solid tumor, then treated with GSE for 2 weeks. The phytochemical analysis of GSE revealed the presence of total phenols (17.442 mg GAE/g) and total flavonoid (6.687 mg CE/g) with antioxidant activity of 81.506 mg TE/g DPPH. The Ehrlich solid tumor significantly raised the activities of ALT, AST, and ALP; the level of alpha fetoprotein (AFP) in serum; and the protein expressions of hepatic proliferating cell nuclear antigen (PCNA) and tumor suppressor protein (P53), as well as induced DNA damage and pathological alterations in liver tissue. However, it significantly reduced serum albumin and total protein levels. In contrast, the co- or post-treatment of EST-bearing mice with GSE reduced the activities of ALT, AST, and ALP; the level AFP in serum; and hepatic P53 and PCNA protein expressions. In addition, it reduced EST-induced hepatic DNA damage and pathological alterations, while it increased serum albumin and total protein levels. This study suggested that GSE is a potent hepatoprotective agent and both co- and post-treatment of EST-bearing mice with GSE almost had the same effects.

Hepatoprotective effect of Thymus vulgaris extract on sodium nitrite-induced changes in oxidative stress, antioxidant and inflammatory marker expression.

The herb thyme (Thymus vulgaris) has multiple therapeutic uses. In this study, we explored how T. vulgaris leaf extract protects liver cells against sodium nitrite-(NaNO2) induced oxidative stress. Mice were divided into four groups; each group received one of the following treatments orally: saline; T. vulgaris extract alone; NaNO2 alone; or T. vulgaris extract + NaNO2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), IL-1ß, IL-6, TNF-α, and total proteins were measured in serum using standard methods. TNF-α, hemooxygenase-1 (HO-1), thioredoxin, SOD, and GSH synthase, all of which are linked to oxidative stress, were measured using quantitative real-time PCR (qRT-PCR). In mice treated with T. vulgaris extract, the effect of NaNO2 on ALT and AST levels and total proteins was reduced, and its effect on antioxidant levels was reversed. Normally, NaNO2 causes hepatocyte congestion and severe hepatic central vein congestion. Tissues in the mice treated with T. vulgaris were restored to normal conditions. Our results demonstrate that NaNO2-induced hepatic injury is significantly reduced by pretreatment with T. vulgaris extract, which protects against hepatic oxidative stress and its associated genes at the 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.

Hypoglycemic and antioxidant effect of Juniperus procera extract on rats with streptozotocin-induced diabetes.

Juniperus procera, a coniferous tree in the cypress family, is one of the famous medicinal plants traditionally used in the southern area of the Arabian peninsula. This study examined the anti-hyperglycemic action of Juniperus procera extract (JPE) on diabetic rats. Sixty male rats were divided into 6 equal groups: control, control treated with JPE (200 mg/kg), diabetic, diabetic treated with insulin (1 U/kg), diabetic treated with JPE (200 mg/kg), and diabetic treated with both insulin and JPE. Blood and tissue samples were collected for serum chemistry, gene expression, and immunohistochemistry analyses, the results of which revealed hyperglycemia and inflammation following diabetes induction. Administration of JPE alone or with insulin reduced the hyperglycemia reported in diabetic rats by 25 %. The immunohistochemical examination of pancreatic tissues demonstrated a moderate restoration of insulin and NF-κB expression in pancreatic and hepatic tissues. Significant recovery was observed for glutathione-S-transferase (GST), superoxide dismutase (SOD), and glutathione peroxidase (GPx) mRNA expression in the livers of rats treated with JPE. Administration of JPE led to similar amelioration of the mRNA expression of pyruvate kinase (PK) and phosphoenol pyruvate carboxy kinase (PEPCK) in the livers of diabetic rats. In addition, diabetic rats treated with insulin, JPE, or a combination of these agents demonstrated an improvement in the mRNA expression of IRS-1 and IRS-2 in hepatic and pancreatic tissues, reaching levels approaching normal. Our findings led us to conclude that JPE has a powerful anti-inflammatory effect accompanied by a moderate hypoglycemic effect that occurs via different mechanisms.

Effect of Taraxacum officinale extract on PI3K/Akt pathway in DMBA-induced breast cancer in albino rats.

BACKGROUND: Breast cancer is one of the most prevalent types of cancer and a leading cause of death in women. MATERIALS AND METHODS: An experimental model of breast cancer was induced in female albino rats using single intragastric dose of 7, 12 dimethylbenz (α) anthracene (DMBA) in sesame oil (50 mg/kg b.wt). Four months after DMBA administration, incidence of breast cancer was confirmed by measuring cancer antigen 15-3 (CA15-3) serum levels. Taraxacum officinale ssp. officinale root extract (TOE) was administered in a dose of 500 mg/kg by oral gavage for 4 weeks after breast cancer incidence. Level of CA15-3 as one of the best known breast tumor markers was elevated in all positive breast cancer rats. The genetic effects of TOE on Pdk1-Akt1-Pik3r1-Map3k1-Erbb2-PIk3ca using semi-quantitative RT-PCR analysis were evaluated. In parallel, histopathological changes and immunohistochemical expression of Bcl2 in mammary gland tissues were examined. RESULTS: Level of CA15-3 was normalized in DMBA group administered TOE for 4 weeks. Administration of DMBA increased expression of Pdk1, Akt1, Pik3r1, Map3k1, Erbb2 and PIk3ca Treatment with TOE normalized the up-regulated mRNA for all examined genes except Pik3ra that was up-regulated. Mammary gland tissues of DMBA group showed excessive proliferation of lining epithelium of acini and ductules with hyperchromatic nuclei with excessive immunostaining of Bcl2 in the proliferated epithelium that was ameliorated by TOE administration. In conclusion, TOE regulated PI3K and Akt pathways involved in suppression of breast cancer growth and proliferation. TOE is effective as anticancer herbal agent.

Effects of Karela (Bitter Melon; Momordica charantia) on genes of lipids and carbohydrates metabolism in experimental hypercholesterolemia: biochemical, molecular and histopathological study.

BACKGROUND: Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Humans seek for safe herbal medication such as karela (Momordica charantia/bitter melon) to treat such disorders to avoid side effect of pharmacotherapies widely used. METHODS: Forty male Wistar rats were divided into four equal groups; control group with free access to food and water, cholesterol administered group (40 mg/kg BW orally); karela administered group (5 g /kg BW orally) and mixture of cholesterol and karela. The treatments continued for 10 weeks. Karela was given for hypercholesterolemic rats after 6 weeks of cholesterol administration. Serum, liver and epididymal adipose tissues were taken for biochemical, histopathological and genetic assessments. RESULTS: Hypercholesterolemia induced a decrease in serum superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and an increase in malondialdehyde (MDA) levels that were ameliorated by karela administration. Hypercholesterolemia up regulated antioxidants mRNA expression and altered the expression of carbohydrate metabolism genes. In parallel, hypercholesterolemic groups showed significant changes in the expression of PPAR-alpha and gamma, lipolysis, lipogenesis and cholesterol metabolism such as carnitine palmitoyltransferase-1 (CPT-1). Acyl CoA oxidase (ACO), fatty acids synthase (FAS), sterol responsible element binding protein-1c (SREBP1c), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and cholesterol 7α-hydroxylase (CYP7A1) at hepatic and adipose tissue levels. Interestingly, Karela ameliorated all altered genes confirming its hypocholesterolemic effect. Histopathological and immunohistochemical findings revealed that hypercholesterolemia induced hepatic tissue changes compared with control. These changes include cholesterol clefts, necrosis, karyolysis and sever congestion of portal blood vessel. Caspase-3 immunoreactivity showed positive expression in hepatic cells of hypercholesterolemic rats compared to control. All were counteracted and normalized after Karela administration to hypercholesterolemic group. CONCLUSION: Current findings confirmed that karela is a potential supplement useful in treatment of hypercholesterolemia and its associated disorders and is good for human health.

Protective effect of grape seed extract against cadmium-induced testicular dysfunction.

Cadmium (Cd) is the most prevalent toxic metal present in livestock feed; therefore, the present study aimed to examine the ameliorative effects of grape seed extract (GSE) on cadmium chloride (CdCl2)­induced testicular dysfunction of Wistar rats. Male adult Wistar rats (40 rats; n=10/group) were divided into four equal groups. Group one was used as a control, and was given ad libitum access to food and water. Groups 2­4 were treated with CdCl2 [5 mg/kg body weight (BW)], GSE (400 mg/kg BW, orally), and GSE plus CdCl2, respectively. Blood and testicular tissues were collected and assayed for biochemical and histopathological changes, respectively. Testicular genes were expressed using semi­quantitative RT­PCR analysis. The results of the present study demonstrated that there was a decrease in serum testosterone levels following CdCl2 toxicity, which were normalized after GSE co-administration. Furthermore, CdCl2 significantly increased the serum levels of malondialdehyde, and decreased levels of antioxidants. At the histopathological level, the testes of the CdCl2 group exhibited congestion, edema in the interstitial blood vessels, irregular arrangement of the epithelial lining of the seminiferous tubules, and degeneration and sloughing of the spermatogenic cells, which accumulated in the center of the seminiferous tubules. Such pathological alterations were ameliorated following treatment with GSE in the CdCl2 plus GSE group. The immunohistochemical expression of B­cell lymphoma 2­associated X protein was high in the CdCl2 group, and low in the control and GSE groups. Co­treatment with GSE and CdCl2 exhibited ameliorative effects on the immunoreactivity of B­cell lymphoma 2­associated X protein. CdCl2 toxicity induced a significant downregulation in the mRNA expression levels of cytochrome P450 cholesterol side­chain cleavage enzyme, cytochrome P450 17A1, 3ß­hydroxysteroid dehydrogenase (3ß­HSD), 17ß­HSD, androgen receptor, steroidogenic acute regulatory protein, and follicle­stimulating hormone receptor. GSE administration exhibited a stimulatory effect on steroidogenesis­associated enzymes, and co­treatment with GSE and CdCl2 normalized and upregulated the mRNA expression levels of these examined genes. This study concluded that GSE has beneficial protective effects against the deleterious effects of CdCl2 on the testis.

Ameliorative effects of pomegranate on carbon tetrachloride hepatotoxicity in rats: A molecular and histopathological study.

The present study aimed to investigate the molecular mechanism underlying the hepatoprotective effects of pomegranate (POM) against oxidative stress in a rat model of carbon tetrachloride (CCl4)-induced liver damage. Injection of rats with CCl4 resulted in hepatic inflammation and lipid accumulation via the upregulation of interleukin (IL)­6 and sterol regulatory element­binding protein 1c (SREBP­1c) mRNA expression. CCl4 induced downregulation of the anti­inflammatory factors alpha 2­macroglobulin (α­2M) and IL­10 in comparison with the POM treated group. In addition, CCl4 induced downregulation of superoxide dismutase (SOD), glutathione S­transferase (GST) and catalase (CAT) expression. Conversely, prior administration of POM counteracted the deleterious alterations induced by CCl4. POM downregulated CCl4-induced IL­6 upregulation, normalized the increase in SREBP­1c expression, and prevented CCl4­induced α­2M downregulation. POM counteracted CCL4­induced alterations via immunosuppressive, anti­inflammatory and regenerative effects by upregulating transforming growth factor­ß1, HSP70 and IL-10 mRNA expression. In addition, POM increased reactive oxygen species scavenging activity by augmenting the antioxidant defense mechanism against CCl4 hepatotoxicity, as demonstrated by detecting SOD, CAT and GST expression. These results confirm that, at the molecular level, POM exerts hepatoprotective effects against CCl4­induced oxidative stress and liver tissue damage.