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1.
Pharmacol Rep ; 72(2): 360-367, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32109309

ABSTRACT

BACKGROUND: Lead is a dangerous systemic toxicant and can provoke life-threatening renal injury. The plan of this study was to evaluate the potential impact of curcumin (CRMN) and L-ascorbic acid (L-ascb) alone or together to counteract lead acetate (Pb-acetate)-induced renal damage in rats and to find out the underlying mechanisms of action of these nutraceuticals. METHODS: Pb-acetate (100 mg/kg/day, i.p.) was injected in male rats along with L-ascb (250 mg/kg/day) and/or CRMN (200 mg/kg/day) orally for 7 days. RESULTS: Pb-acetate administration increased serum urea, creatinine and uric acid. Renal tissue showed a marked depletion in reduced glutathione level and superoxide dismutase activity and elevation in nitric oxide and malondialdehyde levels. Serum C-reactive protein and IL-1ß levels were elevated. Up-regulation of the expression of kidney injury molecule, vascular adhesion molecule-1 and Cystatin C were noticed after Pb-acetate administration. DNA fragmentation was also increased in renal tissues. Histopathological examination revealed a destructed partial layer of Bowman's capsule, proximal and distal convoluted tubules. Treatment with the aforementioned antioxidants ameliorated most of the altered measured biomarker levels. CONCLUSION: Interestingly, the combination of L-ascb and CRMN showed the superlative protective effect against Pb-acetate-induced nephrotoxicity.


Subject(s)
Acute Kidney Injury/prevention & control , Antioxidants/therapeutic use , Cystatin C/genetics , Gene Expression/drug effects , Lead/toxicity , Organometallic Compounds/toxicity , Acute Kidney Injury/chemically induced , Animals , Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Ascorbic Acid/therapeutic use , Cell Adhesion Molecules/genetics , Curcumin/administration & dosage , Curcumin/therapeutic use , Down-Regulation , Drug Synergism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Kidney Function Tests , Male , Rats, Wistar , Vascular Cell Adhesion Molecule-1/genetics
2.
Dose Response ; 17(4): 1559325819885782, 2019.
Article in English | MEDLINE | ID: mdl-31798354

ABSTRACT

BACKGROUND: Lead is a common environmental and occupational pollutant which induced multiorgans dysfunction. The present study was designed to investigate the hepatoprotective effects of turmeric (TUR) and/or vitamin C (Vit-C) alone or together against lead acetate toxicity and to explore novel molecular pathways. METHOD: Acute hepatotoxicity was induced by lead acetate (100 mg/kg/day, i.p.) in male rats, and the effect of TUR (200 mg/kg/day, orally) and/or Vit-C (250 mg/kg/day, orally) along with lead acetate for 7 days was studied. RESULTS: Lead acetate increased serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, hepatic lipid peroxidation and nitric oxide; while, hepatic superoxide dismutase and glutathione activities were downregulated. Hepatic Bcl-2-associated X (Bax) and B-cell lymphoma-2 (Bcl-2) proteins expressions were altered and hepatic DNA damaged was increased as well. Liver/body weight ratio was decreased. Hematoxylin and eosin demonstrated that lead acetate induced focal areas of massive hepatic degeneration of the hepatocytes. Treatment with both antioxidants ameliorated all the altered parameters and induced marked improvement of liver architecture. CONCLUSION: The combination of TUR and Vit-C has shown the most protective effects against lead acetate-induced hepatotoxicity.

3.
Antioxidants (Basel) ; 8(12)2019 Nov 24.
Article in English | MEDLINE | ID: mdl-31771282

ABSTRACT

Arctium lappa L (A. lappa) is a popular medicinal plant with promising hepatoprotective activity. This study investigated the protective effect of A. lappa root extract (ALRE) on lead (Pb) hepatotoxicity, pointing to its ability to modulate oxidative stress, inflammation, and protein kinase B/Akt/glycogen synthase kinase (GSK)-3ß signaling. Rats received 50 mg/kg lead acetate (Pb(Ac)2) and 200 mg/kg ALRE or vitamin C (Vit. C) for 7 days, and blood and liver samples were collected. Pb(Ac)2 provoked hepatotoxicity manifested by elevated serum transaminases and lactate dehydrogenase, and decreased total protein. Histopathological alterations, including distorted lobular hepatic architecture, microsteatotic changes, congestion, and massive necrosis were observed in Pb(II)-induced rats. ALRE ameliorated liver function and prevented all histological alterations. Pb(II) increased hepatic lipid peroxidation (LPO), nitric oxide (NO), caspase-3, and DNA fragmentation, and serum C-reactive protein, tumor necrosis factor-α, and interleukin-1ß. Cellular antioxidants, and Akt and GSK-3ß phosphorylation levels were decreased in the liver of Pb(II)-induced rats. ALRE ameliorated LPO, NO, caspase-3, DNA fragmentation and inflammatory mediators, and boosted antioxidant defenses in Pb(II)-induced rats. In addition, ALRE activated Akt and inhibited GSK-3ß in the liver of Pb(II)-induced rats. In conclusion, ALRE inhibits liver injury in Pb(II)-intoxicated rats by attenuating oxidative injury and inflammation, and activation of Akt/GSK-3ß signaling pathway.

4.
Biomolecules ; 9(11)2019 11 05.
Article in English | MEDLINE | ID: mdl-31694300

ABSTRACT

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3ß signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3ß phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3ß in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3ß. However, further studies scrutinizing the exact role of Akt/GSK-3ß signaling are recommended.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Ascorbic Acid/administration & dosage , Chemical and Drug Induced Liver Injury/drug therapy , Curcumin/administration & dosage , Organometallic Compounds/toxicity , Signal Transduction/drug effects , Alanine Transaminase/blood , Animals , Anti-Inflammatory Agents/pharmacology , Ascorbic Acid/pharmacology , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/metabolism , Curcumin/pharmacology , Disease Models, Animal , Gene Expression Regulation, Enzymologic/drug effects , Glycogen Synthase Kinase 3 beta/metabolism , L-Lactate Dehydrogenase/blood , Male , Oxidative Stress/drug effects , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Wistar
5.
Pharmacol Rep ; 71(6): 1088-1094, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31629938

ABSTRACT

BACKGROUND: Acetamiprid (ACMP) is a member of the neonicotinoid group of insecticides. It is extensively used worldwide. The misuse of ACMP creates danger hazards to human and animal. METHODS: ACMP induced renal damage evidenced by an increase in kidney injury biomarkers. So the goal of this work is to clarify the reno protective effect of Quercetin (Qrctn) and/or Nano-glutathione (N-Gluta) solely or in combination to counterbalance the danger effect of ACMP. All treatments with the previous agents were coadministered orally with ACMP for one month. RESULTS: ACMP ingestion caused a significant rise in serum creatinin, urea, and uric acid, TNF α along with renal cystatin C, lipid peroxidation and nitric oxide with the concomitant decline in the levels of reduced glutathione and IL-10 levels. Protein expression of ICAM was upregulated as well as mRNA expression of NF-κB while mRNA expression of Nrf2 was down-regulated. Immune histochemistry of TLR 4 revealed strong immune reaction. The administration of Qrctn or N-Gluta either individually or together modulated all the preceding aforementioned parameters. CONCLUSION: Fascinatingly Qrctn and N-Gluta combination was the most powerful regimen to frustrate ACMP reno-toxicity and may be deliberate as a hopeful applicant for renal therapy.


Subject(s)
Glutathione/pharmacology , Intercellular Adhesion Molecule-1/metabolism , NF-kappa B/metabolism , Neonicotinoids/toxicity , Quercetin/pharmacology , Toll-Like Receptor 4/metabolism , Animals , Cystatins/metabolism , Glutathione/metabolism , Humans , Interleukin-10/metabolism , Kidney/metabolism , Lipid Peroxidation/drug effects , NF-E2-Related Factor 2/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism
6.
Dose Response ; 17(3): 1559325819871755, 2019.
Article in English | MEDLINE | ID: mdl-31516401

ABSTRACT

The aim of the current study is to assess the effectiveness of milk thistle seeds (Mth) in combination with Taraxacum officinale (Tof) and/or Camellia sinensis (Csin) against tetrachloromethane (Tcm) renotoxicity in rats. Tetrachloromethane was injected in a single dose, followed by 1-month treatments with Mth, Tof, and Csin alone or in combination. Serum urea, uric acid, and creatinine levels were significantly increased matched with the control group. Masson trichrome stain revealed increase in the deposition of fibrous tissue in the interstitium between the tubules and the renal corpuscles. Immunohistochemical analysis of kidney tissues revealed that Tcm induced an increase in the immune response of tumor growth factor ß (TGF-ß) and Janus kinase (JAK) protein expressions and cysteine-aspartic acid protease 3 (caspase 3), while B-cell lymphoma 2 (Bcl2) was downregulated. Treatment with the antioxidants in question either alone or in combination ameliorated all kidney function parameters and showed mild immune reactivity toward TGF-ß and JAK protein expressions in blood vessels and glomeruli in the kidney tissues and downregulated caspase 3 and activated Bcl2 protein expression. The combination regimen of the 3 antioxidants showed the most significant renoprotective effect. This was also confirmed histopathologically. It was concluded that the antioxidant mixture is considered as a promising candidate toward renal dysfunction and immune reactivity induced by Tcm and other toxicants.

8.
Mol Biol Rep ; 46(2): 1955-1962, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30721418

ABSTRACT

There is a significant association exists between vitamin D deficiencies, low respiratory tract infections, and certain types of VDR gene polymorphism. Various studies are being conducted to prove any such link between the different clinical conditions due to disturbed vitamin D regulation and VDR gene polymorphisms. The present study analyzed the presence of vitamin D receptor (VDR) gene polymorphisms (ApaI and TaqI) in Saudi pediatric patient suffering from acute lower respiratory tract infection (ALRTI) cases. Fifty children (50) with ALRTI admitted at King Saud University Medical City, Riyadh/Saudi Arabia were included in addition to seventy-three (73) apparently healthy children who were considered as the control group. Genomic DNA from whole blood was extracted and subjected to polymerase chain reaction (PCR) targeting TaqI and ApaI VDR polymorphisms. RFLP-PCR genotyping was performed to determine the allelic frequency within the VDR gene. In the whole sample, the allelic frequency of ApaI polymorphism in the VDR gene was 58.5%, 17.9%, and 23.6% for AA, Aa, and aa respectively (p = 0.11), while it was 48%, 19%, and 33% for TT, Tt, and tt respectively (p = 0.33) with regards to the frequency of TaqI polymorphism in the VDR gene. VDR ApaI Aa and aa genotypes and VDR TaqI Tt and tt genotypes were not associated with increased risk of ALRTI in children (OR 0.87, 95% CI 0.33-2.28, p = 0.77; OR 0.56, 95% CI 0.23-1.4, p = 0.21; OR 1.15, 95% CI 0.44-2.99, p = 0.77; OR 0.73, 95% CI 0.32-1.68, p = 0.46 respectively). To conclude, neither vitamin D status nor VDR gene polymorphisms such as ApaI and TaqI is associated with increased susceptibility to ALRTI. Linkage disequilibrium was not detected between ApaI and TaqI VDR gene polymorphisms as in the case of serum vitamin D status in ALRTI patients versus apparent healthy children.


Subject(s)
Receptors, Calcitriol/genetics , Respiratory Tract Infections/genetics , Vitamin D/metabolism , Case-Control Studies , Child , Child, Preschool , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Infant , Linkage Disequilibrium , Male , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide , Receptors, Calcitriol/metabolism , Respiratory Tract Infections/blood , Respiratory Tract Infections/metabolism , Saudi Arabia , Vitamin D/blood , Vitamin D/genetics , Vitamin D Deficiency/genetics
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