Biochemical, molecular and cytological impacts of alpha-lipoic acid and Ginkgo biloba in ameliorating testicular dysfunctions induced by silver nanoparticles in rats.

Silver nanoparticles (AgNPs) are commonly utilized in medicine. However, they have negative effects on the majority of organs, including the reproductive system. AgNPs were reported to be able to reach the testicular tissues due to their nano size, which allows them to pass through blood-testicular barriers. The goal of this study was to see if alpha-lipoic acid (LA) or Ginkgo biloba (GB) might protect adult rat testes after intraperitoneal injection of AgNPs. Forty male healthy adult Wister albino rats were randomly assigned to four groups: control, AgNPs-intoxicated group intraperitoneally injected AgNPs 50 mg/kg b.w, 3 times a week; LA + AgNPs group intoxicated with AgNPs and orally gavaged with 100 mg LA/kg b.w; and GB + AgNPs group injected with AgNPs and orally given GB extract 120 mg/kg b.w for 30 consecutive days. Biochemical changes (testosterone, ACP, and prostatic acid phosphatase), oxidative indices, mRNA expression of proapoptotic (BAX) and anti-apoptotic (BCL-2) biomarkers, histological, and immunohistochemical changes in testicular tissues were investigated. Significant decrease in serum testosterone level and elevation in ACP and PACP enzyme activity in AgNPs-treated rats. As well, there were lowering in tGSH, GSH GR, GPx, and elevation in MDA and GSSG values. AgNPs-exposed rats expressed downregulation of testicular thirodexin-1 (Txn-1), transforming growth factor-1ß (TGF-1ß), anti-apoptotic (BCL-2), and upregulaion of proapoptotic biomarkers (BAX) mRNA expressions. Strong positive action to BAX and lowering the action of Ki-67 antibody were observed. Because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with LA or GB could be beneficial in reducing the harmful effects of AgNPs on the testicles.

2, 3-Dimethylsuccinic acid and fulvic acid attenuate lead-induced oxidative misbalance in brain tissues of Nile tilapia Oreochromis niloticus.

Lead has long been known as neurotoxic and immunotoxic heavy metal in human and animals including fish, whereas, 2, 3-dimethylsuccinic acid (DMSA) and fulvic acid (FA) are well-known biological chelators. The present investigation was carried out to assess the potential chelating and antioxidant effects of dietary supplementation with DMSA and FA against lead acetate (Pb)-induced oxidative stress in Nile tilapia, O. niloticus. One-hundred and eighty apparently healthy O. niloticus fish (30 ± 2.5 g) were allocated into six equal groups. The first group was fed on basal diet and served as control, while the second group was fed on DMSA-supplemented basal diets at levels of 30 mg/kg diet; the third group was fed on FA-supplemented basal diet at level of 0.3 mg/kg diet; the forth, fifths, and sixth groups were exposed to 14.4 mg Pb /L water (1/10 LC50) and feed on basal diet only, basal diet supplemented with DMSA (0.3 mg/kg diet), or basal diet supplemented with FA (0.3 mg/kg diet), respectively. Antioxidant and lipid peroxidative status, activity of glucose 6-phosphate dehydrogenase (G6PD), and lactate dehydrogenase (LDH) as well as the histopathologic findings were evaluated in brain tissues, while the Pb residues were evaluated in liver, muscles, and brain tissues. The results of the present study showed that DMSA and FA decreased malondialdehyde (MDA) and Pb residue in tissues of Pb-exposed fish and improved the histologic picture and brain contents of glutathione (GSH), glutathione-s-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), G6PD, LDH, and total antioxidant capacity (TAC). It could be concluded that DMSA and FA supplementation exhibited potential neuroprotective effect against Pb-induced oxidative brain damages in O. niloticus through improvement of antioxidant status of the brain tissue.

Quercetin Attenuates Brain Oxidative Alterations Induced by Iron Oxide Nanoparticles in Rats.

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.

Date palm fruit extract ameliorated pancreatic apoptosis, endocrine dysfunction and regulatory inflammatory cytokines in Streptozotocin-induced diabetes in rats.

The current work studied the mechanism(s) and ability by which date palm (Phoenix dactylifera L.) fruit extract (DPE) inspired a glucose-lowering impact in rats suffering from diabetes. Forty-eight albino rats were divided into six various experimental treatments after induction of diabetes by intraperitoneal infusion of streptozotocin (45 mg/kg bwt) as follows: normal control, DPE, diabetic control, diabetic glibenclamide (GLI), diabetic DPE, and diabetic GLI plus DPE-treated groups. In animals euthanized after 8 weeks, blood and pancreatic tissue samples were assembled to assess different biochemical and histopathological changes. The expressions of insulin, B cell lymphoma-2 (Bcl-2), and cysteine aspartate-specific protease-3 (caspase-3) in islet ß cells were also evaluated using immunohistochemical assessment. Diabetic rats exhibited hyperglycemia; increment of pancreatic malondialdehyde (lipid peroxidation biomarker), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß); and decrement of plasma insulin and pancreatic antioxidants: glutathione, superoxide dismutase, and catalase values. Also, the pancreatic islets exhibited histopathological and morphometric alternations associated with weak positive insulin and Bcl-2 immunoreactivity and strong positive caspase-3 immunoreactivity. DPE and/or GLI, an anti-diabetic drug, improved the pancreatic histoarchitecture and improved ß cell function and structure, which increased insulin levels and improved the insulin, Bcl-2, and caspase-3 immunoreactivity in diabetic rats. Nevertheless, the combined DPE and GLI therapy revealed a significant recovery and restoration of ß cells' structure and function. The date palm fruit has anti-apoptotic, anti-inflammatory, and antioxidant activities and hypoglycemic effects, which in turn play a pivotal role in avoiding the progression of diabetes mellitus. Moreover, it could potentiate the glucose-lowering activity of anti-diabetic drugs.

Apoptosis and astrogliosis perturbations and expression of regulatory inflammatory factors and neurotransmitters in acrylamide-induced neurotoxicity under ω3 fatty acids protection in rats.

This study was aimed to investigate the potential ameliorative effects of omega-3 (ω3) fatty acids against acrylamide (ACR)-induced neurotoxicity. Thirty-two adult male Sprague Dawley rats were randomly assigned into four groups (n = 8) as follows: control, ω3 fatty acids (1000 mg/kg bwt/day orally), ACR-treated (50 mg/kg bwt/day IP) and ACR plus ω3 fatty acids group. Treatments were performed every other day for 21 consecutive days. ACR induced abnormal gait and elevated serum levels of proinflammatory cytokines (IL-6 and TNF-α), brain and spinal cord MDA levels and decreased brain and spinal cord GSH levels. Moreover, it reduced neurotransmitters (acetylcholine, GABA, serotonin and noradrenaline levels) and increased AChE activity in brain tissues. Histopathologically, ACR caused various degenerative changes, necrosis and glial cell activation in the cerebrum, cerebellum, hippocampus, spinal cord and sciatic nerve. Likewise, the histomorphometric analysis was constant with ACR-induced neurotoxicity. The ACR induced axonal atrophy and myelin disruption and decreased g-ratio of the sciatic nerve. Immunohistochemically, strong positive expressions of apoptotic marker caspase-3 and astroglial GFAP in the examined tissues were detected. Contrariwise, concurrent administration of ω3 fatty acids partially attenuated ACR impacts, as it improved the gait performance, reduced oxidative stress and pro-inflammatory cytokines, and modulate the levels of the neurotransmitters. It also ameliorated the intensity of ACR-induced histopathological and histomorphometric alterations within the examined nervous tissues. It could be concluded that ω3 fatty acids have antioxidant, anti-inflammatory and anti-apoptotic potentials against ACR neurotoxicity via suppression of oxidative stress, lipid peroxidation and pro-inflammatory cytokines, and inhibition of AChE activity and downregulation of caspase-3 and GFAP expressions in the nervous tissues.

Attenuation potentials of royal jelly against hydroxyurea-induced infertility through inhibiting oxidation and release of pro-inflammatory cytokines in male rats.

Hydroxyurea (HDU), a class of antineoplastic drugs, has a powerful efficacy in the treatment of several types of malignancies. However, it has multiple adverse effects including reduced fertility, especially in males. Thus, 60 male albino rats were used to investigate the chemoprotective potentials of royal jelly on HDU-induced testicular damage. Animals were gastro-gavaged with HDU (225 or 450 mg kg-1 bw day-1) before royal jelly (100 mg kg-1 bw day-1) for 60 days. Blood samples and testicles were collected, and spermatozoon was obtained. In a dose-dependent manner, the sperm count, motility and liveability, and testosterone, GSH, and catalase concentrations were decreased in HDU groups, whereas MDA, FSH, LH, IL-6, and IFN-γ expression levels were increased. Germinal epithelium degeneration, germ cell sloughing, reduction in the number of luminal spermatozoa, interstitial congestion, and severe leukocyte infiltration besides no glandular secretion in most of the acini were identified. However, royal jelly intake in HDU-treated rats successfully improved sperm quality, hormonal and antioxidant status, and reproductive organ histoarchitecture. Thus, it could be concluded that royal jelly is endowed with antioxidative and anti-inflammatory activities and could be, therefore, used as an adjuvant remedy to improve HDU-induced male subfertility.

Antioxidant activities of Moringa oleifera leaf extract against pendimethalin-induced oxidative stress and genotoxicity in Nile tilapia, Oreochromis niloticus (L.).

To assess the ameliorative effects of Moringa oleifera (MO) leaf extract on haematological and biochemical changes, liver DNA damage and oxidative stress biomarkers in Nile tilapia (Oreochromis niloticus) exposed to a sublethal concentration (0.52 mg/l) of pendimethalin (PM). Tilapia fish were allocated into four equal groups in tri-replicates as follows: first group was the control group, second group was treated with MO (20 ml/30 l water), third group was exposed to 0.52 mg PM/l and fourth group was exposed to 0.52 mg PM/l and treated with MO leaf extract (20 ml/30 l water) for 28 days. At the end of this period, blood and liver tissue samples were collected and haematological and biochemical changes, hepatic DNA fragmentation and oxidative stress biomarkers were analysed. Pendimethalin caused significant reduction in haematological profile [White blood cells (WBCs) and red blood cells (RBCs) counts, haemoglobin (Hb) concentration and haematocrit (Ht) level]; meanwhile, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, uric acid, glucose, cortisol, cholesterol and lactate dehydrogenase (LDH) were significantly increased. On the other hand, serum total protein, albumin, globulin and acetylcholinesterase (AChE) were decreased. Significant reduction in hepatic superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC) and glutathione peroxidase (GSH-Px) levels and marked increments of hepatic malondialdehyde (MDA) and DNA fragmentation were observed in PM-exposed fish compared to the control group. The addition of Moringa oleifera leaf extract into the water could overcome the negative impacts of pendimethalin and normalise the examined parameters nearly to the control values. Moringa oleifera was used for the first time to protect tilapia fish against PM-induced toxicity. The present study revealed that Moringa oleifera has potent antioxidant and antigenotoxic actions against pendimethalin toxicity.

Papaya extract upregulates the immune and antioxidants-related genes, and proteins expression in milk somatic cells of Friesian dairy cows.

Carica papaya is a perennial plant containing bioactive constituents with free radical-scavenging and immune-modulating activities. In contrast, the immune suppression is predominant in the periparturient period, where oxidative stress has a substantial impact on the mammary gland health. The aim of the experiment reported here was to determine the potential effect of C. papaya aqueous extract (CPE) on milk production traits, and expression of genes and proteins related to immune and antioxidant status in dairy milk somatic cells (MSCs). Forty Friesian dairy cows were divided equally between a control and CPE-treated groups (orally drenched 250 µg/kg bwt, once weekly a month before expected parturition and continued until 5 months post-partum). CPE did not affect milk yield or composition but upregulated the expression of ß13-defensin (DEFB13), cathelicidin 2 (CATHL2), cathelicidin antimicrobial peptide (CATHL3), hepcidin (HAMP), lysozyme (LYZ), catalase (CAT) and glutathione peroxidase (GSH-Px) in MSCs. The environmental micro-organisms did not influence the levels of the transcripts. The DEFB13, CATHL2, CATHL3, HAMP and LYZ, but not ß1-defensin (DEFB1) transcripts and proteins were constitutively expressed in MSCs obtained from pathogen-free udders. It could be concluded that CPE has immunostimulant and antioxidant activities; thereby, it could be utilized to minimize the occurrence of mastitis.

Curcumin and quercetin synergistically attenuate subacute diazinon-induced inflammation and oxidative neurohepatic damage, and acetylcholinesterase inhibition in albino rats.

The ubiquitous use of diazinon (DZN, an organophosphorus insecticide) has increased the probability of occupational, public, and the ecosystem exposure; these exposures are linked to negative health outcomes. The flavonoids curcumin (CUR) and quercetin (QUE) exert significant anti-inflammatory and antioxidant activities against toxicants, including insecticides. However, it is unclear whether their combination enhances these activities. Therefore, 40 albino rat were divided randomly into the CTR, DZN, CUR + DZN, QUE + DZN, and CUR + QUE + DZN groups, which are treated daily via gavage for 28 days. DZN induced neurohepatic inflammation and oxidative damage, which was confirmed by significant (P < 0.05) induction of aspartate and alanine aminotransferases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase, and tumor necrosis factor-α and inhibition of acetylcholinesterase activity. Furthermore, the liver and brain of DZN-exposed rats exhibited a notable elevation in MDA level paralleled with reduction in antioxidant molecules, i.e., glutathione, superoxide dismutase, glutathione peroxidase, and catalase. The pretreatment of DZN-intoxicated rats with CUR or QUE substantially mitigated neurohepatic dysfunction and inflammation and improved liver and brain antioxidant status with reducing oxidative stress levels. Furthermore, pretreatment with CUR + QUE synergistically restored the neurohepatic dysfunction and oxidative levels to approximately normal levels. The overall results suggested that CUR or QUE inhibits DZN-mediated neurohepatic toxicity via their favorable anti-inflammatory, antioxidant, and free radical-scavenging activities. Moreover, both QUE and CUR may be mutual adjuvant agents against oxidative stress neurohepatic damages.

Potential role of α-lipoic acid and Ginkgo biloba against silver nanoparticles-induced neuronal apoptosis and blood-brain barrier impairments in rats.

AIMS: This study explored whether silver nanoparticles (AgNPs) can disrupt tight-junctions integrity resulted in blood-brain barrier dysfunction along with oxidative stress, pro-inflammation, and apoptosis induction. Additionally, neuroprotective activities of α-lipoic acid (LA) and Ginkgo biloba (GB) were investigated. MAIN METHODS: Forty adults rats were enrolled into; Control, AgNPs (50 mg/kg), LA (100 mg/kg) + AgNPs, and GB (120 mg/kg) + AgNPs. After 30 days, neuronal changes were assessed biochemically and histopathologically. Brain tissues oxidative indices, mRNA expression of proinflammatory cytokines and tight-junction proteins and pro-apoptotic biomarker, caspase-3 were investigated. KEY FINDINGS: AgNPs exposure enhanced lipid peroxidation (+195%) along with declines in glutathione (-43%), glutathione peroxidase (-34%), glutathione S-transferase (-31%), catalase (-43%), and superoxide dismutase (-38%) activities in brain tissues. The apparent brain oxidative damage was associated with obvious neuronal dysfunction that was ascertained by neuropathological lesions. AgNPs lowered serum acetylcholine esterase, iron and copper levels, and increased creatine phosphokinase and creatine phosphokinase-brain type activities. Following AgNPs exposure, brain silver and iron contents were increased, but the copper level was decreased. AgNPs up-regulated TNF-α (6.5-fold) and IL-1ß (8.9-fold) transcript levels, and simultaneously over-expressed the caspase-3 protein in cerebrum and cerebellum inducing cell apoptosis. Moreover, AgNPs down-regulated the transcript levels of tight-junction proteins; JP-1 (0.65-fold) and JAM-3(0.81-fold). SIGNIFICANCE: LA and relatively GB improved the serious effects of AgNPs on the blood-brain barrier function and tight-junction proteins through their antioxidants, anti-inflammatory, and anti-apoptotic efficacies. Co-treatment with LA or GB may be favorable in ameliorating the neurotoxic side effects of AgNPs.

Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation.

AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, SP (500 mg/kg bwt, oral gavage daily for 21 days), MTX (20 mg/kg bwt, single ip injection), and MTX+SP. Hepatic and splenic histoarchitecture, leukocyte counts and serum immunoglobulins were evaluated. Hepatic oxidant/antioxidant status, proinflammatory cytokines (tumor necrosis factor-α, and interleukin 6), and pro-apoptotic proteins (caspase 3 and Bax) immunoexpression were assessed. KEY FINDINGS: MTX induced extensive hepatic necrosis and vacuolation, and sever lymphoid depletion in splenic white pulp with increased levels of serum transaminases, lactate dehydrogenase, and hepatic malondialdehyde, tumor necrosis factor-α and interleukin 6; and number of caspase 3- and Bax-positive hepatocytes. A significant decrease in leukocyte counts, serum immunoglobulins (IgA, IgM and IgG) level, and hepatic antioxidant enzymes (GSH, GPx, SOD, and CAT) was also detected. Pretreatment with SP resulted in significant improvements in hepatic and splenic histologic architecture, as well as restoring liver enzymes and reduction of lipid peroxidation product, proinflammatory cytokines, and caspase 3 and Bax immunoexpression. Additionally, a significant increase in antioxidant enzymes, serum immunoglobulins, and total leukocyte counts was demonstrated. SIGNIFICANCE: SP possesses promising antioxidant, anti-inflammatory, anti-apoptotic and immune stimulatory properties against MTX-induced hepatotoxicity and immunosuppression.

Impact of diesel exhaust exposure on the liver of mice fed on omega-3 polyunsaturated fatty acids-deficient diet.

Exposure to diesel exhaust (DE) exacerbates non-alcoholic fatty liver disease, and may systemically affect lipid metabolism. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have anti-inflammatory activity and suppresses hepatic triacylglycerol accumulation, but many daily diets are deficient in this nutrient. Therefore, the effect of DE exposure in mice fed n-3 PUFA-deficient diet was investigated. Mice were fed control chow or n-3 PUFA-deficient diet for 4 weeks, then exposed to clean air or DE by inhalation for further 4 weeks. Liver histology, plasma parameters, and expression of fatty acid synthesis-related genes were evaluated. N-3 PUFA-deficient diet increased hepatic lipid droplets accumulation and expression of genes promoting fatty acid synthesis: Acaca, Acacb, and Scd1. DE further increased the plasma leptin and the expression of fatty acid synthesis-related genes: Acacb, Fasn, and Scd1. N-3 PUFA-deficient diet and DE exposure potentially enhanced hepatic fatty acid synthesis and subsequently accumulation of lipid droplets. The combination of low-dose DE exposure and intake of n-3 PUFA-deficient diet may be an additional risk factor for the incidence of non-alcoholic fatty liver disease. The present study suggests an important mechanism for preventing toxicity of DE on the liver through the incorporation of n-3 PUFAs in the diet.

Hepatoprotective efficacy of Spirulina platensis against lead-induced oxidative stress and genotoxicity in catfish; Clarias gariepinus.

Lead (Pb) is a toxic environmental pollutant that induces a broad range of biochemical and physiological hazards in living organisms. We investigated the possible hepatoprotective effects of Spirulina platensis (SP) in counteracting the Pb-induced oxidative damage. Ninety-six adult African catfish were allocated into four equal groups. The 1st group (control) fed basal diet while the 2nd group (Pb-treated) fed on basal diet and exposed to 1mg Pb(NO3)2/L. The 3rd and 4th groups fed SP-supplemented basal diets at levels of 0.25% and 0.5%, respectively and exposed to Pb. Serum samples were used to analyze hepatic function biomarkers, electrolytes, and oxidant and antioxidant status. Lipid peroxidation and DNA fragmentation were determined in the liver tissues. Pb exposure induced hepatic dysfunction, electrolytes (Na+, K+, Ca+2, and Cl-) imbalance, as well a significant decrease in GSH content, and LDH, AChE, SOD, CAT and GST enzymes activity. SP supplementation reverted these biochemical and genetic alterations close to control levels. This amelioration was higher with 0.5% SP and at the 4th week of exposure, showing concentration- and time-dependency. Thus, the current study suggests that SP could protect the catfish liver against lead-induced injury by scavenging ROS, sustaining the antioxidant status and diminishing DNA oxidative damage. The dietary inclusion of SP can be used as a promising protective agent to counteract oxidative stress-mediated diseases and toxicities.

Hepatoprotective efficacy of Nigella sativa seeds dietary supplementation against lead acetate-induced oxidative damage in rabbit - Purification and characterization of glutathione peroxidase.

Lead (Pb) is a toxic ubiquitous environmental pollutant that induces hepatotoxicity in both animals and humans. The ability of Nigella saliva seeds (NSS) in ameliorating lead acetate (PbAc)-induced hepatic oxidative damage was investigated using a rabbit model. Forty New Zealand rabbits were given feed and water ad libitum. They were allocated randomly into four groups: control; PbAc (5g/L drinking water); NSS (20g/kg diet) and NSS+PbAc groups. After two months, liver samples were collected and analyzed for malondialdehyde (MDA), glutathione (GSH), glutathione S-transferase (GST) and glutathione peroxidase (GPx) contents. Purification and characterization of GPx were also evaluated. PbAc exposure significantly (p<0.05) increased MDA (lipid peroxidation biomarker) and reduced the GSH levels and the GST and GPx activities. Concurrently supplemented NSS significantly (p<0.05) decreased MDA levels and restored the GSH, GST, and GPx contents successfully. Electrophoretically, the homogeneous GPx preparation from the liver had a specific activity of 30.44 U/mg protein and a yield of 1.31%. The Km values for cumene hydroperoxide were 4.76µM in control, PbAc and NSS+PbAc groups, and 4.09µM in NSS group. The GPx reaction had a temperature optimum 40°C, pH optimum 8 and molecular weight 21 kDa. The obtained data indicated the potent efficacy of NSS against PbAc-induced oxidative stress; that was mediated through induction and activation of antioxidants, particularly GPx and scavenging free radicals. Moreover, the purified hepatic GPx is characterized as a selenoprotein (Se-GPx).

Nephroprotective efficacy of ceftriaxone against cisplatin-induced subchronic renal fibrosis in rats.

Cisplatin, or cis-diamminedichloridoplatinum(II), (CDDP) is a broad-spectrum antineoplastic chemotherapeutic agent with a potent efficacy against several malignancies. Its main clinical antineoplastic therapy-limiting adverse effect is nephrotoxicity, where the developments of effective nephroprotectors are needed. Therefore, the present study aimed to investigate the nephroprotective and antifibrotic potential of ceftriaxone (CTX) against CDDP-induced toxicity. Male Wister rats were treated with saline or CTX (100 or 200 mg kg-1 bw) an hour before CDDP administration (1 mg kg-1 bw). All the treatments were intraperitoneally administered twice weekly for consecutive 10 weeks. Twenty-four hours after last CDDP dose, blood samples were collected, then the animals were euthanized and their kidneys were isolated for measurements. CDDP significantly increased serum uric acid, urea, and creatinine contents. Toxicopathic changes showed that CDDP induced marked tubulointerstitial damage, overexpressed fibrogenic factors α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1), and down expressed cellular proliferating biomarker bromodeoxyuridine (BrdU). CTX pretreatment, particularly 200 mg/kg bw, improved the renal function biomarkers; histoarchitecture; and α-SMA, TGF-ß1, and BrdU expressions. It could be concluded that CTX is endowed with antifibrotic properties and could be, therefore, used as adjuvant therapy to improve CDDP-induced nephrotoxicity. Further clinical researches are necessary to evaluate whether CTX may exhibit a new therapeutic choice for treating renal fibrotic diseases.

Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies.

Diazinon (DZN) is a common organophosphorus insecticide extensively used for agriculture and veterinary purposes. DZN toxicity is not limited to insects; it also induces harmful effects in mammals and birds. Our experiment evaluated the protective and antioxidant potential of sesame oil (SO) and (or) alpha-lipoic acid (ALA) against DZN toxicity in male Wistar albino rats. DZN-treated animals exhibited macrocytic hypochromic anemia and significant increases in serum biochemical parameters related to liver injury, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γGT), cholesterol, and triglycerides. They also had elevated levels of markers related to cardiac injury, such as lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and increased biomarkers of renal injury, urea and creatinine. DZN also increased hepatic, renal, and cardiac lipid peroxidation and decreased antioxidant biomarker levels. SO and (or) ALA supplementation ameliorated the deleterious effects of DZN intoxication. Treatment improved hematology and serum parameters, enhanced endogenous antioxidant status, and reduced lipid peroxidation. Importantly, they exerted synergistic hepatoprotective, nephroprotective, and cardioprotective effects. Our findings demonstrate that SO and (or) ALA supplementation can alleviate the toxic effects of DZN via their potent antioxidant and free radical-scavenging activities.

Vitamin C modulates cadmium-induced hepatic antioxidants' gene transcripts and toxicopathic changes in Nile tilapia, Oreochromis niloticus.

Cadmium (Cd) is one of the naturally occurring heavy metals having adverse effects, while vitamin C (L-ascorbic acid) is an essential micronutrient for fish, which can attenuate tissue damage owing to its chain-breaking antioxidant and free radical scavenger properties. The adult Nile tilapia fish were exposed to Cd at 5 mg/l with and without vitamin C (500 mg/kg diet) for 45 days in addition to negative and positive controls fed with the basal diet and basal diet supplemented with vitamin C, respectively. Hepatic relative mRNA expression of genes involved in antioxidant function, metallothionein (MT), glutathione S-transferase (GST-α1), and glutathione peroxidase (GPx1), was assessed using real-time reverse transcription polymerase chain reaction (RT-PCR). Hepatic architecture was also histopathologically examined. Tilapia exposed to Cd exhibited upregulated antioxidants' gene transcript levels, GST-⍺1, GPx1, and MT by 6.10-, 4.60-, and 4.29-fold, respectively. Histopathologically, Cd caused severe hepatic changes of multifocal hepatocellular and pancreatic acinar necrosis, and lytic hepatocytes infiltrated with eosinophilic granular cells. Co-treatment of Cd-exposed fish with vitamin C overexpressed antioxidant enzyme-related genes, GST-⍺1 (16.26-fold) and GPx1 (18.68-fold), and maintained the expression of MT gene close to control (1.07-fold), averting the toxicopathic lesions induced by Cd. These results suggested that vitamin C has the potential to protect Nile tilapia from Cd hepatotoxicity via sustaining hepatic antioxidants' genes transcripts and normal histoarchitecture.

Chicory (Cichorium intybus L.) root extract regulates the oxidative status and antioxidant gene transcripts in CCl4-induced hepatotoxicity.

The ability of Cichorium intybus root extract (chicory extract) to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity was evaluated in male rats. The rats were divided into four groups according to treatment: saline (control); chicory extract (100 mg/kg body weight daily, given orally for 2 weeks); CCl4 (1 ml/kg body weight by intraperitoneal injection for 2 consecutive days only); or chicory extract (100 mg/kg body weight daily for 2 weeks) + CCl4 injection on days 16 and 17. The levels of hepatic lipid peroxidation, antioxidants, and molecular biomarkers were estimated twenty-four hours after the last CCl4 injection. Pretreatment with chicory extract significantly reduced CCl4-induced elevation of malondialdehyde levels and nearly normalized levels of glutathione and activity of glutathione S-transferase, glutathione peroxidase (GPx), glutathione reductase, catalase (CAT), paraoxonase-1 (PON1), and arylesterase in the liver. Chicory extract also attenuated CCl4-induced downregulation of hepatic mRNA expression levels of GPx1, CAT and PON1 genes. Results of DNA fragmentation support the ability of chicory extract to ameliorate CCl4-induced liver toxicity. Taken together, our results demonstrate that chicory extract is rich in natural antioxidants and able to attenuate CCl4-induced hepatocellular injury, likely by scavenging reactive free radicals, boosting the endogenous antioxidant defense system, and overexpressing genes encoding antioxidant enzymes.