scholarly journals Effect of Reynoutria Japonic and Resveratrol on Sirt1/SOD/MDA of Adriamycin-Induced Renal Injury: A Randomised Trial

2021 ◽  
Author(s):  
Shangmei Cao ◽  
xiaojing liu ◽  
xinxin sun ◽  
xixia chen ◽  
shuifu Tang
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Kidney Injury ◽  
Group Model ◽  
Mrna Levels ◽  
Model Group ◽  
Drug Induced ◽  
Blank Group ◽  
Reynoutria Japonica ◽  
Comparison Results

Abstract Background: Mechanisms of drug-induced kidney injury include mitochondrial dysfunction and oxidative stress. Resveratrol is a natural activator of sirt1 that is related to oxidative stress.Objectives: To explore the mechanism of treating drug-induced kidney injury with Reynoutria japonica and its extract (Resveratrol).Methods: Fifty adult male SD rats were randomly divided into five groups: blank group, model group, Reynoutria japonica group, resveratrol group and Benazepril group. Except the blank group, each group used a one-time tail vein injection of 7.5mg/kg adriamycin to make the rat model of drug-induced renal injury. After three days, the proteinuria test strip showed green, which was positive for proteinuria. Each group was given the corresponding drug. ACR was measured on the seventh day every week. All rats were anaesthetized death on the fourth weekend to obtain blood and kidneys. Results: At the fourth week, the MDA levels of blank group and Reynoutria japonica group were significantly lower than those of benazepril hydrochloride group (P<0.05), and the MDA levels of resveratrol group and model group were significantly higher than those of benazepril hydrochloride group (P<0.05).The Sirt1 mRNA levels of the blank group and the Reynoutria japonica group were significantly higher than those in the benazepril hydrochloride group (P<0.05), and the Sirt1 mRNA levels of resveratrol group and model group were significantly lower than those of the benazepril hydrochloride group (P<0.05). The comparison results between groups of the Sirt1 protein expression were the same as those of the Sirt1 mRNA expression (P<0.05).Conclusions: The therapeutic effect of the Reynoutria japonica group was better than that of the Benazepril group and resveratrol group.

Effect of Reynoutria Japonica and its Extract on Sirt1 in Cisplatin-Induced Renal Injury

2021 ◽  
Author(s):  
Shangmei Cao ◽  
Xiaojing Liu ◽  
Xinxin sun ◽  
Xixia Chen ◽  
Shuifu Tang
Keyword(s):  
Oxidative Stress ◽  
Treatment Group ◽  
Protein Expression ◽  
Kidney Injury ◽  
Model Group ◽  
Drug Induced ◽  
Blank Group ◽  
Reynoutria Japonica ◽  
Gene And Protein Expression ◽  
Sirt1 Gene

Abstract Background: Mechanisms of drug-induced kidney injury include mitochondrial dysfunction and oxidative stress. Resveratrol is a natural activator of sirt1 that is related to oxidative stress.Aim: To explore the mechanism of treating drug-induced kidney injury with Reynoutria japonica and its extract (Resveratrol).Design: Fifty adult male SD rats were randomly divided into five groups: blank group, model group, Reynoutria japonica group, resveratrol group and lotensin group. Each group was given the corresponding drug. ACR was measured on the seventh day every week. Creatinine and urea nitrogen were measured on the fourth weekend. All rats were sacrificed on the fourth weekend to detect the relevant indicators in the kidney.Results: At the fourth week, the ACR, Scr and BUN of the Resveratrol group were higher than those of the lotensin group and Reynoutria japonica group (P<0.05). The values of Scr and BUN were lower in the Reynoutria japonica group than in the lotensin group (P<0.05). The levels of SOD, NO, and sirt1 gene and protein expression in the model group and treatment group were lower than those in the blank group, and those in the model group were lower than those in the treatment group (P<0.05). The levels of SOD, NO, and sirt1 gene and protein expression in the Reynoutria japonica group were higher than the lotensin group (P<0.05).Conclusions: The therapeutic effect of the Reynoutria japonica group was better than that of the lotensin group and resveratrol group.

scholarly journals Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 572
Author(s):  
Jung-Yeon Kim ◽  
Jungmin Jo ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Renal Injury ◽  
Manganese Superoxide Dismutase ◽  
Immune Cell ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Pleiotropic Effects ◽  
Induced Apoptosis ◽  
Vascular Adhesion

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.

scholarly journals Antioxidant Activity, Phenolic Profile, and Nephroprotective Potential of Anastatica hierochuntica Ethanolic and Aqueous Extracts against CCl4-Induced Nephrotoxicity in Rats

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2973
Author(s):  
Tariq I. Almundarij ◽  
Yousef M. Alharbi ◽  
Hassan A. Abdel-Rahman ◽  
Hassan Barakat
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Therapeutic Agent ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Total Phenolic ◽  
Drug Induced ◽  
Total Carotenoids ◽  
Phenolic Profile ◽  
Better Than

Kaff-e-Maryam (Anastatica hierochuntica L.) is extensively used to treat a range of health problems, most notably to ease childbirth and alleviate reproductive system-related disorders. This study aimed to evaluate the effect of A. hierochuntica ethanolic (KEE), and aqueous (KAE) extracts on CCl4-induced oxidative stress and nephrotoxicity in rats using the biochemical markers for renal functions and antioxidant status as well as histopathological examinations of kidney tissue. A. hierochuntica contained 67.49 mg GAE g−1 of total phenolic compounds (TPC), 3.51 µg g−1 of total carotenoids (TC), and 49.78 and 17.45 mg QE g−1 of total flavonoids (TF) and total flavonols (TFL), respectively. It resulted in 128.71 µmol of TE g−1 of DPPH-RSA and 141.92 µmol of TE g−1 of ABTS-RSA. A. hierochuntica presented superior antioxidant activity by inhibiting linoleic acid radicals and chelating oxidation metals. The HPLC analysis resulted in 9 and 21 phenolic acids and 6 and 2 flavonoids in KEE and KAE with a predominance of sinapic and syringic acids, respectively. Intramuscular injection of vit. E + Se and oral administration of KEE, KAE, and KEE + KAE at 250 mg kg−1 body weight significantly restored serum creatinine, urea, K, total protein, and albumin levels. Additionally, they reduced malondialdehyde (MOD), restored reduced-glutathione (GSH), and enhanced superoxide dismutase (SOD) levels. KEE, KAE, and KEE + KAE protected the kidneys from CCl4-nephrotoxicity as they mainly attenuated induced oxidative stress. Total nephroprotection was about 83.27%, 97.62%, and 78.85% for KEE, KAE, and KEE + KAE, respectively. Both vit. E + Se and A. hierochuntica extracts attenuated the histopathological alteration in CCl4-treated rats. In conclusion, A. hierochuntica, especially KAE, has the potential capability to restore oxidative stability and improve kidney function after CCl4 acute kidney injury better than KEE. Therefore, A. hierochuntica has the potential to be a useful therapeutic agent in the treatment of drug-induced nephrotoxicity.

scholarly journals Toxicologic Pathology Forum Opinion Paper*: Recommendations for a Tiered Approach to Nonclinical Mechanistic Nephrotoxicity Evaluation

2018 ◽  
Vol 46 (6) ◽  
pp. 636-646 ◽  
Author(s):  
Daniela Ennulat ◽  
Michael Ringenberg ◽  
Kendall S. Frazier
Keyword(s):  
Renal Injury ◽  
Kidney Injury ◽  
Mechanistic Study ◽  
Potential Mechanism ◽  
Drug Induced ◽  
Additional Hypothesis ◽  
Tiered Approach ◽  
Road Map ◽  
New Information ◽  
Microscopic Evaluation

Nephrotoxicity is one of the more common causes of attrition in nonclinical drug development. Like most tissues, the kidney has a limited number of ways of responding to toxicological insults from diverse mechanistic pathways, which can limit the ability to determine mechanisms of renal injury using the assays routinely performed in preclinical toxicologic studies. In situations where the renal injury is unusual in morphology or if a therapeutic margin is low, additional investigative techniques may be needed to identify a potential mechanism of toxicity in order to inform clinical risk assessment or establish human relevance and translatability of the toxicity. While routine microscopic evaluation can suggest a specific pathogenesis, understanding the mechanism of renal injury often requires additional hypothesis-driven investigations and specialized techniques to obtain the data necessary to identify a nephrotoxic mechanism. Nonclinical mechanistic investigations can be resource-intensive and often yield limited new information. Although there are multiple avenues to investigate renal toxicity, no single mechanistic study or prescriptive battery of tests will identify the pathophysiologic basis for every potential mechanism of renal injury. To aid the nonclinical investigator, we outline a tiered approach for prioritizing investigations to provide a rational and linear road map for the exploration of mechanisms of drug-induced kidney injury. [Box: see text]

scholarly journals TNF-α in T lymphocytes attenuates renal injury and fibrosis during nephrotoxic nephritis

2020 ◽  
Vol 318 (1) ◽  
pp. F107-F116 ◽  
Author(s):  
Yi Wen ◽  
Nathan P. Rudemiller ◽  
Jiandong Zhang ◽  
Taylor Robinette ◽  
Xiaohan Lu ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Renal Injury ◽  
Kidney Injury ◽  
Mrna Levels ◽  
T Helper ◽  
T Helper 17 ◽  
Immune Mediated ◽  
Tnf Α ◽  
Lymphocyte Responses

Nephrotoxic serum nephritis (NTN) models immune-mediated human glomerulonephritis and culminates in kidney inflammation and fibrosis, a process regulated by T lymphocytes. TNF-α is a key proinflammatory cytokine that contributes to diverse forms of renal injury. Therefore, we posited that TNF-α from T lymphocytes may contribute to NTN pathogenesis. Here, mice with T cell-specific deletion of TNF-α (TNF TKO) and wild-type (WT) control mice were subjected to the NTN model. At 14 days after NTN, kidney injury and fibrosis were increased in kidneys from TNF TKO mice compared with WT mice. PD1+CD4+ T cell numbers and mRNA levels of IL-17A were elevated in NTN kidneys of TNF TKO mice, suggesting that augmented local T helper 17 lymphocyte responses in the TNF TKO kidney may exaggerate renal injury and fibrosis. In turn, we found increased accumulation of neutrophils in TNF TKO kidneys during NTN. We conclude that TNF-α production in T lymphocytes mitigates NTN-induced kidney injury and fibrosis by inhibiting renal T helper 17 lymphocyte responses and infiltration of neutrophils.

scholarly journals Effect of Heweianshen Decoction on Orexin-A and Cholecystokinin-8 Expression in Rat Models of Insomnia

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Fagen Li ◽  
Shaodan Li ◽  
Yi Liu ◽  
Ke Cao ◽  
Minghui Yang
Keyword(s):  
Rat Model ◽  
Wistar Rats ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Orexin A ◽  
Blank Group ◽  
Rat Models ◽  
Male Wistar Rats

Objective. To study the effect of Heweianshen decoction (HAD) on orexin-A and cholecystokinin-8 (CCK-8) expression in rat models of insomnia caused by injecting parachlorophenylalanine (PCPA) intraperitoneally.Methods. Fifty male Wistar rats were randomly divided into five groups (10 rats in each group): blank group, model group, and low-, medium-, and high-dose HAD-treated groups. A rat model of insomnia was established by injecting intraperitoneally with PCPA (300 mg/kg body weight). Rats were given normal saline (10 mL/kg) or 5.25, 10.5, and 21 g/kg HAD by intragastric administration once a day for 6 days. After that, the rats were sacrificed to collect the hypothalamus for tests, using radioimmunoassay to detect the expression of orexin-A and CCK-8.Results. Heweianshen decoction reduced the expression of orexin-A and increased the expression of CCK-8 in the hypothalamus of rat model of insomnia.Conclusion. The therapeutic effect of HAD on insomnia is partially attributed to the decreased expression of orexin-A and increased expression of CCK-8.

scholarly journals Protective Effects of Ulva lactuca Polysaccharide Extract on Oxidative Stress and Kidney Injury Induced by D-Galactose in Mice

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 539
Author(s):  
Qian Yang ◽  
Yanhui Jiang ◽  
Shan Fu ◽  
Zhaopeng Shen ◽  
Wenwen Zong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Oxidative Damage ◽  
Renal Injury ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Ulva Lactuca ◽  
Protective Mechanism ◽  
Serum Cystatin C ◽  
Apoptotic Protein

Reactive oxygen species (ROS) are the key factors that cause many diseases in the human body. Polysaccharides from seaweed have been shown to have significant antioxidant activity both in vivo and in vitro. The ameliorative effect of Ulva lactuca polysaccharide extract (UPE) on renal injury induced by oxidative stress was analyzed. As shown by hematoxylin–eosin staining results, UPE can significantly improve the kidney injury induced by D-galactose (D-gal). Additionally, the protective mechanism of UPE on the kidney was explored. The results showed that UPE could decrease the levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Cys-C), lipid peroxidation, protein carbonylation, and DNA oxidative damage (8-OHdG) and improve kidney glutathione content. Moreover, UPE significantly increased the activities of superoxide dismutase and glutathione peroxidase and total antioxidant activity in mice. UPE also decreased the levels of inflammatory cytokines TNF-α and IL-6. Further investigation into the expression of apoptotic protein caspase-3 showed that UPE decreased the expression of apoptotic protein caspase-3. These results indicate that UPE has a potential therapeutic effect on renal injury caused by oxidative stress, providing a new theoretical basis for the treatment of oxidative damage diseases in the future.

scholarly journals Administration of N-acetylcysteine Plus Acetylsalicylic Acid Markedly Inhibits Nicotine Reinstatement Following Chronic Oral Nicotine Intake in Female Rats

2021 ◽  
Vol 14 ◽  
Author(s):  
María Elena Quintanilla ◽  
Paola Morales ◽  
Fernando Ezquer ◽  
Marcelo Ezquer ◽  
Mario Herrera-Marschitz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Prefrontal Cortex ◽  
Acetylsalicylic Acid ◽  
Female Rats ◽  
Mrna Levels ◽  
Drug Induced ◽  
Nicotine Intake ◽  
Valuable Adjunct ◽  
Oral Nicotine

BackgroundNicotine is the major addictive component of cigarette smoke and the prime culprit of the failure to quit smoking. Common elements perpetuating the use of addictive drugs are (i) cues associated with the setting in which drug was used and (ii) relapse/reinstatement mediated by an increased glutamatergic tone (iii) associated with drug-induced neuroinflammation and oxidative stress.AimsThe present study assessed the effect of the coadministration of the antioxidant N-acetylcysteine (NAC) plus the anti-inflammatory acetylsalicylic acid (ASA) on oral nicotine reinstatement intake following a post-deprivation re-access in female rats that had chronically and voluntarily consumed a nicotine solution orally. The nicotine-induced oxidative stress and neuroinflammation in the hippocampus and its effects on the glutamate transporters GLT-1 and XCT mRNA levels in prefrontal cortex were also analyzed.ResultsThe oral coadministration of NAC (40 mg/kg/day) and ASA (15 mg/kg/day) inhibited by 85% of the oral nicotine reinstatement intake compared to control (vehicle), showing an additive effect of both drugs. Acetylsalicylic acid and N-acetylcysteine normalized hippocampal oxidative stress and blunted the hippocampal neuroinflammation observed upon oral nicotine reinstatement. Nicotine downregulated GLT-1 and xCT gene expression in the prefrontal cortex, an effect reversed by N-acetylcysteine, while acetylsalicylic acid reversed the nicotine-induced downregulation of GLT-1 gene expression. The inhibitory effect of N-acetylcysteine on chronic nicotine intake was blocked by the administration of sulfasalazine, an inhibitor of the xCT transporter.ConclusionNicotine reinstatement, following post-deprivation of chronic oral nicotine intake, downregulates the mRNA levels of GLT-1 and xCT transporters, an effect reversed by the coadministration of N-acetylcysteine and acetylsalicylic acid, leading to a marked inhibition of nicotine intake. The combination of these drugs may constitute a valuable adjunct in the treatment of nicotine-dependent behaviors.

scholarly journals Purified Sika deer antler protein attenuates GM-induced nephrotoxicity by activating Nrf2 pathway and inhibiting NF-κB pathway

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhenyi Wang ◽  
Lulu Wang ◽  
Jing Wang ◽  
Jiacheng Luo ◽  
Haonan Ruan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Sika Deer ◽  
Kidney Injury ◽  
Annexin V ◽  
Expression Level ◽  
Hek293 Cells ◽  
Protective Effects ◽  
Deer Antler ◽  
Drug Induced

Abstract Although gentamicin is widely used as an antibiotic in clinical practice, it also has some side-effects, such as acute kidney injury, which is a common condition caused by the abuse of gentamicin. Sika deer antler protein (SDAPR) can antagonize drug-induced AKI. Since SDAPR is recognized as an effective part of velvet antler, its components were further separated. Two components named SDAP1 and SDAP2 were obtained. The protective effects of SDAPR, SDAP1 and SDAP2 on GM-induced cytotoxicity to HEK293 and its potential mechanisms were studied. MTT and xCELLigence Real-Time cell analysis showed that SDAPR, SDAP1 and SDAP2 could protect HEK293 cells from GM toxicity. Similarly, SDAPR, SDAP1 and SDAP2 can reduce ROS level, reduce oxidative stress and improve inflammation Further studies have shown that SDAPR, SDAP1 and SDAP2 upregulate the Nrf2/HO-1 pathway by increasing the expression of Nrf2 and HO-1, and down-regulate the NF-κB pathway by reducing the protein expression of NF-κB. Annexin V/PI flow cytometry and Hoechst 33258 staining showed that SDAPR, SDAP1 and SDAP2 inhibited GM-induced apoptosis in HEK293 cells. Western blot analysis showed SDAPR, SDAP1 and SDAP2 decreased expression level of Bax and Cleaved-caspase-3, and increased the expression level of Bcl-2. In addition, we examined the feasibility of SDAP1 and SDAP1 to avoid kidney injury in a GM mouse model. In conclusion, SDAPR, SDAP1 and SDAP2 can be used to prevent GM-induced HEK293 cytotoxicity, probably because they have strong anti-oxidative stress, anti-inflammatory and anti-apoptotic effects. And SDAP1 and SDAP2 can inhibit GM-induced acute kidney injury in mice.

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