Hepatoprotective Effect of Ethanolic Pomegranate Peel Extract Against Levofloxacin via Suppression of Oxidative Stress, Proinflammation, and Apoptosis in Male Rats.

One of the fluoroquinolone antibiotics, levofloxacin (LEV), is used to treat a variety of illnesses leading to oxidative stress and cellular damage. Peel from Punica granatum is a waste product abundant in phytochemicals with various biological activities. This study aimed to evaluate P. granatum peel extract's (PGPE) potential to mitigate oxidative stress, inflammation, apoptosis, and liver damage caused by LEV. There were four groups of rats: control, PGPE, LEV, and PGPE + LEV, respectively, and they were orally administered their daily treatments for 2 weeks. Results revealed that PGPE has a large number of phytochemical components with high antioxidant activity. PGPE intake alone enhanced the antioxidant status and decreased oxidative stress. On the other hand, pretreatment of the LEV group with PGPE restored oxidative stress, antioxidant enzymes, glutathione content, liver function biomarkers, and hematological parameters. Also, normalization of gene expressions (cyclooxygenase-2, transforming growth factor-beta1, caspase-3, heme oxygenase-1, B cell lymphoma-2, interleukin [IL]-10, and IL-1) and improvement in liver architecture, and immunohistochemical alpha-smooth muscle actin, were seen in comparison to the LEV group. Conclusively, PGPE exhibits strong anti-inflammatory, antiapoptotic, and antioxidant properties that shield rat liver from the damaging effects of LEV and offer a fresh viewpoint on the application of fruit waste products.

Echinacea purpurea root extract mitigates hepatotoxicity, genotoxicity, and ultrastructural changes induced by hexavalent chromium via oxidative stress suppression.

Environmental and occupational exposure to hexavalent chromium (CrVI) is mostly renowned as a possible hepatotoxic in mammals. Echinacea purpurea (L.) Moench, a phenolic-rich plant, is recurrently used for its therapeutic properties. Therefore, this investigation was done to explore whether E. purpurea (EP) root extract would have any potential health benefits against an acute dose of CrVI-induced oxidative damage and hepatotoxicity. Results revealed that GC-MS analysis of EP root extract has 26 identified components with a significant amount of total phenolic and flavonoid contents. Twenty-four Male Wistar rats were divided into four groups: control, EP (50 mg/kg BW/day for 21 days), CrVI (15 mg/kg BW as a single intraperitoneal dosage), and EP + CrVI, respectively. Rats treated with CrVI displayed a remarkable rise in oxidative stress markers (TBARS, H2O2, PCC), bilirubin, and lactate dehydrogenase activity, and a marked decrease in enzymatic and non-enzymatic antioxidants, transaminases, and alkaline phosphatase activities, and serum protein level. Also, CrVI administration induced apoptosis and inflammation in addition to histological and ultrastructural abnormalities in the liver tissue. The examined parameters were improved significantly in rats pretreated with EP and then intoxicated with CrVI. Conclusively, EP had a potent antioxidant activity and could be used in the modulation of CrVI-induced hepatotoxicity.

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum-induced oxidative stress, hyperlipidemia, and genotoxicity.

BACKGROUND: Aluminum (Al) is a ubiquitous element with proven nephrotoxicity. Silymarin (SM) is a mixture of polyphenolic components extracted from Silybum marianum and exhibited protective influences. However, SM bioactivity can be enhanced by its incorporation in chitosan (CS) through the use of nanotechnology. This work proposed to assess the protective influence of SM and its loaded chitosan nanoparticles (SM-CS-NPs) on aluminum chloride (AlCl3)-induced nephrotoxicity. METHODS: Six groups were created randomly from 42 male Wistar rats and each one contains 7 rats (n = 7). Group I, acted as a control and received water. Group II received SM (15 mg/kg/day) and group III administered with SM-CS-NPs (15 mg/kg/day). Group IV received AlCl3 (34 mg/kg) and groups V and VI were treated with SM and SM-CS-NPs with AlCl3 respectively for 30 days. RESULTS: AlCl3 administration significantly elevated TBARS, H2O2, and kidney function levels besides LDH activity. Whereas GSH, CAT, SOD, GPx, GST, and GR values were all substantially reduced along with protein content, and ALP activity. Additionally, significant alterations in lipid profile, hematological parameters, and renal architecture were observed. Moreover, TNF-α, TGF-ß, and MMP9 gene expression were upregulated in kidney tissues. The administration of SM or its nanoparticles followed by AlCl3 intoxication attenuated renal dysfunction replenished the antioxidant system, and downregulated TNF-α, TGF-ß, and MMP9 gene expression in renal tissues compared to the AlCl3 group. CONCLUSION: SM-CS-NPs have more pronounced appreciated protective effects than SM and have the proficiency to balance oxidant/antioxidant systems in addition to their anti-inflammatory effect against AlCl3 toxicity.

Citrus reticulata peel extract mitigates oxidative stress and liver injury induced by abamectin in rats.

The prevalent use of abamectin (ABM) has latterly raised safety attention as it has different toxicities to non-target living organisms. Citrus fruits are widely renowned for their nutritional and health-promoting qualities, and their peels are full of phenolic constituents. The purpose of the current study was to evaluate the modulatory effectiveness of Citrus reticulata peel extract (CPE) against abamectin-induced hepatotoxicity and oxidative injury. Rats were distributed into 4 groups as follows: control, CPE (400 mg/kg bw orally for 14 days), ABM (2 mg/kg bw for 5 days), and CPE + ABM at the doses mentioned above. Results revealed that GC-MS analysis of CPE has 19 identified components with significant total phenolic and flavonoid contents. Treatment with ABM in rats displayed significant variations in enzymatic and non-enzymatic antioxidants, oxidative stress markers (MDA, H2O2, PCC), liver and kidney function biomarkers, hematological parameters, lipids, and protein profile as well as histopathological abnormalities, inflammation and apoptosis (TNF-α, Caspase-3, NF-κB, and Bcl-2 genes) in rats' liver. Supplementation of CPE solo dramatically improved the antioxidant state and reduced oxidative stress. C. reticulata peel extract pretreatment alleviated ABM toxicity by modulating most of the tested parameters compared to the ABM group. Conclusively, CPE had potent antioxidant activity and could be used in the modulation of ABM hepatotoxicity presumably due to its antioxidant, anti-inflammatory, and gene-regulating capabilities.

Hepatoprotective impact of Nigella sativa silver nanocomposite against genotoxicity, oxidative stress, and inflammation induced by thioacetamide.

Protection from liver damage and the repercussion of that harm is thought to be crucial for reducing the number of deaths each year. This work was developed to evaluate the possible role of silver nanocomposite prepared using Nigella sativa (N. sativa) aqueous extract against the hepatic damage brought on by thioacetamide (TAA), with particular attention to how they affect the NF-κß, TNF-α, IL-1ß, and COX-2 signaling pathways. There were seven groups of male Wistar rats used as follows: control, saline, N. sativa aqueous extract (NSAE; 200 mg/kg/d), N. sativa silver nanocomposite (NS-AgNC; 0.25 mg/kg/d), TAA (100 mg/kg; thrice weekly), NSAE + TTA, and NS-AgNC + TAA, respectively. The experiment continued for six weeks. The results showed that NS-AgNPs significantly enhanced liver functions (p<0.05) (albumin, ALP, LDH, AST, total protein, ALT, and globulin) and oxidant/antioxidant biomarkers (p<0.05) (H2O2, MDA, PCC, NO, SOD, CAT, GPx, GR, GST and, GSH), contrasted with TAA group. Moreover, a significant (p<0.05) downregulation of the gene expressions (COX-2, TNF-α, IL-1ß, and NF-κß) was also achieved by using silver nanocomposite therapy. These findings have been supported by histological analysis. Collectively, NS-AgNC exhibits more prominent and well-recognized protective impacts than NSAE in modulating the anti-inflammatory, genotoxicity and oxidative stress effects against TAA-induced liver injuries.

Punica granatum (Pomegranate) Peel Extract Pre-Treatment Alleviates Fenpropathrin-Induced Testicular Injury via Suppression of Oxidative Stress and Inflammation in Adult Male Rats.

Fenpropathrin (FNP) is one of the commonly used insecticides in agriculture and domestically, leading to environmental and health problems. The goal of the current investigation was to determine how well pomegranate peel extract (PGPE) could prevent the testicular toxicity and oxidative stress induced by FNP. Four groups of male Wistar rats were randomly assigned: negative control (corn oil), PGPE (500 mg/kg BW), positive control (FNP; 15 mg/kg BW, 1/15 LD50), and PGPE + FNP. For four weeks, the rats received their doses daily and orally via gavage. The major phytochemical components (total phenolic, flavonoids, and tannins contents) detected in PGPE by GC-MS included ellagic acid, hydroxymethylfurfurole, guanosine, and pyrogallol with high total phenolic, flavonoids, and tannin contents. FNP-treated rats showed a marked elevation in testicular levels of thiobarbituric acid-reactive substances, hydrogen peroxide, and protein carbonyl content, as well as the activity of aminotransferases and phosphatases. Meanwhile. a significant decline in body weight, gonadosomatic index, glutathione, protein contents, enzymatic antioxidants, and hydroxysteroid dehydrogenase (3ß HSD, and 17ß HSD) activity was observed. In addition, significant alterations in testicular P53, Cas-3, Bcl-2, IL-ß, IL-10, testosterone, follicle-stimulating and luteinizing hormones, and sperm quality were detected. Furthermore, biochemical and molecular changes were corroborated testicular histological abnormalities. Moreover, PGPE-pretreated FNP-intoxicated rats demonstrated considerable improvement in the majority of the studied parameters, when compared to FNP-treated groups. Conclusively, PGPE provided a potent protective effect against the testicular toxicity caused by FNP, due to its antioxidant-active components.

Nephroprotective role of Echinacea purpurea against potassium dichromate-induced oxidative stress, inflammation, and apoptosis in rats.

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with the overproduction of free radicals, which induces oxidative damage. Echinacea purpurea (L.) Moench is an herbaceous perennial plant rich in phenolic components and frequently used for its medicinal benefits. The current work evaluated the effectiveness of E. purpurea (EP) against oxidative stress and nephrotoxicity induced by potassium dichromate in male rats. Male Wistar rats were divided into four groups: control, E. purpurea (EP; 50 mg/kg; once daily for 3 weeks), hexavalent chromium (Cr(VI); 15 mg/kg; single intraperitoneal dose), and EP + Cr(VI) where rats were pretreated with EP for 3 weeks before receiving CrVI, respectively. Results revealed that rats exposed to Cr(VI) showed a significant increase in PC, TBARS, and H2 O2 , kidney function biomarkers (Urea, creatinine, and uric acid), lactate dehydrogenase activity (LDH), TNF-α, IL-18, nuclear factor kappa B (NFκB), and IGF-1 (Insulin-like growth factor-1) levels as well as a considerable decline in metallothionein (MT), glutathione (GSH) content, enzymatic antioxidants (SOD, CAT, GPx, GR, and GST), alkaline phosphatase (ALP) activities, and protein content. Cr(VI) induced apoptosis in kidney tissues as revealed by upregulation of Bax and caspase 3 and downregulation of Bcl-2. Furthermore, EP treatment ameliorated the Cr(VI)-induced histopathological and ultrastructure variations of kidney tissue, which was confirmed by the biochemical and molecular data. It is clear from the results of this study that EP exerts nephroprotective effects by improving the redox state, suppressing inflammatory reaction and cell apoptosis as well as ameliorating the performance of kidney tissue architecture, which is eventually reflected by the improvement of kidney function in rats.

Hepatoprotective Effect of Actinidia deliciosa against Streptozotocin-Induced Oxidative Stress, Apoptosis, and Inflammations in Rats.

The present research intended to assess the possible protective and hypoglycemic effect of Actinidia deliciosa fruit aqueous extract (ADAE) in diabetic rats. The scavenging antioxidant capabilities of ADAE were evaluated using GC-MS analysis. In addition, rats were divided into four groups: control, ADAE, streptozotocin-induced DM (STZ), and STZ-treated rats + ADAE in an in vivo investigation. GC-MS analysis of ADAE was shown to include major components with high total phenolic contents and high DPPH scavenging activity. In diabetic rats, significant elevation in blood glucose level, lipid peroxidation, bilirubin, and lactate dehydrogenase activity as well as a change in lipid profile was observed, while insulin, body and liver weights, enzymatic and nonenzymatic antioxidants, liver function biomarkers, and protein content were significantly decreased. Furthermore, changes in the expression of the peroxisome proliferator-activated receptor (PPAR-γ), apoptotic, and inflammation-related genes were found. In addition, histological differences in rat liver tissue architecture were discovered, corroborating the biochemical modifications. However, consuming ADAE alone reduced lipid peroxidation and improved antioxidant status. Furthermore, diabetic rats given ADAE showed significant reductions in oxidative stress indicators and biochemical parameters, as well as improved tissue structure, when compared to the diabetic rats' group. Also, ADAE supplementation protects diabetic rats' hepatic tissue by upregulating PPAR-γ and downregulating apoptotic and inflammatory-related gene expression. In conclusion, A. deliciosa has beneficial protective effects so, it might be used as a complementary therapy in diabetes mellitus.

Rosmarinus officinalis essential oil modulates renal toxicity and oxidative stress induced by potassium dichromate in rats.

BACKGROUND: Chromium hexavalent (CrVI) is known as a toxic contaminant that induced oxidative stress and nephrotoxicity in humans and animals. Rosmarinus officinalis is a perennial herb rich in biologically active constituents that have powerful antioxidant properties. So, the current work evaluated the effectiveness of Rosmarinus officinalis essential oil (REO) against alterations induced by potassium dichromate in the kidney of male rats. METHODS: GC-MS analysis, in vitro total phenol contents, and DPPH scavenging activity of REO were estimated. Thirty-five Wistar male rats were categorized into 5 groups. The first group was the control, the second one was orally administered rosemary essential oil (REO; 0.5 mL/kg BW), the third group was injected intraperitoneally with hexavalent chromium (CrVI; 2 mg/kg BW) for 14 days, the fourth group used as the protective group (REO was administrated 30 min before i.p. injection of CrVI) and the fifth group applied as the therapeutic group (rats injected with CrVI 30 min followed by oral administration of REO), respectively. RESULTS: Twenty-nine components were detected with high total phenolic contents and high DPPH scavenging activity. Results revealed that CrVI- intoxicated rats showed a valuable increase in oxidative stress profile (TBARS and H2O2) and a notable decline in glutathione (GSH), total protein content, and enzymatic antioxidants (SOD, CAT, GPx, and GST). Furthermore, serum kidney functions biomarkers (urea, creatinine, and uric acid) were increased significantly. Also, the administration of CrVI showed histological and immunohistochemical (PCNA-ir) changes in rat kidney tissue. Otherwise, administration of REO pre or post-treatment with CrVI significantly restored most of the biochemical parameters in addition to improvement in kidney tissue architecture. Moreover, individual intake with REO exhibited an amendment in oxidative stress markers. CONCLUSION: Conclusively, REO had a potential antioxidant capacity in ameliorating K2Cr2O7-induced nephrotoxicity, especially in the protection group.

Panax ginseng modulates oxidative stress, DNA damage, apoptosis, and inflammations induced by silicon dioxide nanoparticles in rats.

Silicon dioxide nanoparticles (SiO2 NPs) are extensively used in cosmetics, food, and drug delivery. The main mechanism of SiO2 NPs toxicities depends on oxidative stress. Ginseng (Panax ginseng Meyer) is used in various medicinal applications because of its antioxidant efficiency. Therefore, the present study was carried out to investigate the possible combated role of ginseng against SiO2 NPs toxicity in rat liver. Thirty-five male rats (160-180 g) were allocated into five groups of seven rats each, randomly. The first group was used as a control while groups 2, 3, 4, and 5 were treated orally with ginseng (Gin; 75 mg/kg, 1/10 LD50 ), SiO2 NPs, (200 mg/kg, 1/10 LD50 ), Gin + SiO2 NPs (protection group), and SiO2 NPs + Gin (therapeutic group) for 5 weeks, respectively. Treatment with SiO2 NPs increased lipid peroxidation, liver function enzymes, and decreased antioxidant enzymes (SOD, CAT, GPx, GST) activity and non-enzymatic antioxidant (GSH) level. SiO2 NPs administration motivated liver apoptosis as revealed by the upregulation of the apoptotic genes, Bcl2-associated x protein (Bax), and Beclin 1 and downregulation of the anti-apoptotic gene, B-cell lymphoma 2 (Bcl2) as well as increase in DNA damage. Also, SiO2 NPs administration caused inflammation as indicated by upregulation of the inflammation-related genes (interleukin 1 beta [IL1ß], tumor necrosis factor-alpha [TNFα], nuclear factor kappa B [NFκB], cyclooxygenase 2 [Cox2], transforming growth factor-beta 1 [TGFß1]) as well as cell cycle arrest in the G0/G1 phase of liver cells. Moreover, histopathological examination proved the biochemical and molecular perturbations occurred due to SiO2 NPs toxicity. On the other hand, ginseng caused a significant modulation on the deleterious effects induced by SiO2 NPs in rat liver. In conclusion, ginseng has a potent preventive effect than the therapeutic one and might be used in the treatment of SiO2 NPs hepatotoxicity.

Hepatoprotective potential of Rosmarinus officinalis essential oil against hexavalent chromium-induced hematotoxicity, biochemical, histological, and immunohistochemical changes in male rats.

Hexavalent chromium (Cr VI) is widely known as a potential hepatotoxic in humans and animals and its toxicity is associated with oxidative stress. So, an in vivo study was outlined to assess the protective and therapeutic role of Rosmarinus officinalis essential oil (rosemary; REO) against Cr VI-induced hepatotoxicity. Male Wistar rats were assigned into five equal groups (1st group served as control; 2nd and 3rd groups received 0.5 ml/kg BW REO and 2 mg/kg BW Cr VI, respectively; 4th group pretreated with REO then injected with K2Cr2O7; and 5th group received Cr VI then treated with REO for 3 weeks). Results revealed that rats exposed to Cr VI showed a valuable changes in hematological parameters and an increase in oxidative stress markers (Protein carbonyl, TBARS, and H2O2) and a noteworthy decline in glutathione (GSH) content. Furthermore, a considerable decrease in enzymatic antioxidants (SOD, CAT, GPx, and GST), transaminases (AST and ALT), and alkaline phosphatase (ALP) activities, as well as total protein and albumin levels, was detected, while serum liver function biomarkers were increased significantly. In addition, the evaluation of histopathological and immunohistochemical PCNA expression showed significant variations in the liver that confirm the biochemical results. Administration of REO pre- or post-chromium treatment restored the parameters cited above near to the normal values. Otherwise, individual intake with REO slumped lipid peroxidation and gotten better antioxidant status significantly. Conclusively, REO proved to be an effective antioxidant in modulating Cr VI-induced hepatotoxicity, especially in the pretreated rats.

Ocimum basilicum Essential Oil Modulates Hematotoxicity, Oxidative Stress, DNA Damage, and Cell Cycle Arrest Induced by ß-cyfluthrin in Rat Liver.

Pesticides are used in large quantities infrequently, resulting in environmental damage and health issues. The goal of the current study was to explore the ameliorating effect of Ocimum basilicum (Basil) leaves essential oil versus the harmful effects of ß-cyfluthrin in rat liver. Male Wistar rats were classified at random into four groups; negative control (corn oil), basil leaves essential oil (BEO, 3 ml/kg), ß-cyfluthrin (positive control) (ß-Cyf; 15 mg/kg BW, 1/25 LD50), and BEO plus ß-Cyf, respectively. The rats were given their doses orally every day for a month. Results revealed that BEO yielded 6.32 mg/g with 33 identified components, representing 97% of the total oil. BEO implicated a considerable level of total phenolic contents, DPPH radical scavenging capacity, ABTS activity, and FRAP. The treatment of ß-Cyf dramatically elevated lipid peroxidation (TBARS and H2O2) (LPO), protein oxidation (PC, AOPP, and HYP), and considerably reduced enzymatic (SOD, CAT, GPx, GR, and GST) and non-enzymatic (GSH) antioxidants. After ß-Cyf treatment, hematological parameters, body and liver weights, enzyme activity (AST, ALT, ALP, and LDH), as well as protein, albumin, globulin, and total bilirubin levels were all considerably affected. Furthermore, ß-Cyf increased the expression of pro-inflammatory genes (TNF-α, IL-6) as well as DNA damage and cell cycle arrest in the G0/G1 phase and decreased the number of cells in S and G2/M phase of liver cells. Moreover, rats given BEO then intoxicated with ß-Cyf showed substantial changes in the majority of the parameters tested. Finally, BEO was shown to have high antioxidant efficacy in combating ß-Cyf toxicity because of its high phenolic content.