Protective effect of pentoxifylline on oxidative renal cell injury associated with renal crystal formation in a hyperoxaluric rat model

Öztürk, Hayrettin; Çetinkaya, Ayhan; Fırat, Tülin; Tekçe, Buket Kın; Düzcü, Selma Erdoğan; Öztürk, Hülya

doi:10.1007/s00240-018-1072-8

Cited by 15 publications

(29 citation statements)

References 50 publications

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“…CaOx crystal was indicated to induce the oxidative stress of kidney. The modulation of oxidative stress could ameliorate the crystal-induced renal injury [38,39]. These were verified by detecting ROS in the kidney tissues.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic analysis reveals a protective effect of Fu-Fang-Jin-Qian-Chao herbal granules on oxalate-induced kidney injury

et al. 2019

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Nephrolithiasis is one of the world’s major public health burdens with a high incidence and a risk of persistent renal dysfunction. Fu-Fang-Jin-Qian-Chao granules (FFJQC), a traditional Chinese herb formula, is commonly used in treatment of nephrolithiasis. However, the therapeutic mechanism of FFJQC on kidney stone has still been a mystery. The objective of the present study is to explore the therapeutic mechanism of FFJQC on kidney injury and identify unique metabolomics patterns using a mouse model of kidney stone induced by a calcium oxalate (CaOx) deposition. Von Kossa staining and immuno-histopathological staining of osteopontin (OPN), cluster of differentiation 44 (CD44) and calbindin-D28k were conducted on renal sections. Biochemical analysis was performed on serum, urine, and kidney tissues. A metabolomics approach based on ultra-HPLC coupled with quadrupole-TOF-MS (UHPLC-Q-TOF/MS) was used for serum metabolic profiling. The immunohistopathological and biochemical analysis showed the therapeutic benefits of FFJQC. The expression levels of OPN and CD44 were decreased while calbindin-D28k increased after the CaOx injured mice were treated with FFJQC. In addition, total of 81 serum metabolites were identified to be associated with protective effects of FFJQC on CaOx crystal injured mice. Most of these metabolites were involved in purine, amino acid, membrane lipid and energy metabolism. Potential metabolite biomarkers were found for CaOx crystal-induced renal damage. Potential metabolite biomarkers of CaOx crystal-induced renal damage were found. FFJQC shows therapeutic benefits on CaOx crystal injured mice via regulation of multiple metabolic pathways including amino acids, purine, pyrimidine, glycerolipid, arachidonic acid (AA), sphingolipid, glycerophospholipid, and fatty acid.

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Section: Discussionmentioning

confidence: 99%

Metabolomic analysis reveals a protective effect of Fu-Fang-Jin-Qian-Chao herbal granules on oxalate-induced kidney injury

et al. 2019

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“…The exact mechanisms of stone formation have not been identified; however, it is known that approximately 80% of kidney stones contain CaOx and one of the most common causes of CaOx stones is hyperoxaluria [1,22]. Oxalate is a by-product of normal metabolism, eliminated from the body under normal conditions [20].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Quercetin on Oxidative Stress-Induced Tubular Epithelial Damage in the Experimental Rat Hyperoxaluria Model

et al. 2021

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Background and Objectives: The most common kidney stones are calcium stones and calcium oxalate (CaOx) stones are the most common type of calcium stones. Hyperoxaluria is an essential risk factor for the formation of these stones. Quercetin is a polyphenol with antioxidant, anti-inflammatory, and many other physiological effects. The aim of this study was to investigate the protective effect of quercetin in hyperoxaluria-induced nephrolithiasis. Materials and Methods: Male Wistar-Albino rats weighing 250–300 g (n = 24) were randomized into three groups: Control (n = 8), ethylene glycol (EG) (n = 8), and EG + quercetin (n = 8). One percent EG-water solution was given to all rats except for the control group as drinking water for five weeks. Quercetin-water solution was given to the EG + quercetin group by oral gavage at a dose of 10 mg/kg/day. Malondialdehyde (MDA), catalase (CAT), urea, calcium, and oxalate levels were analyzed in blood and urine samples. Histopathological assessments and immunohistochemical analyses for oxidative stress and inflammation indicators p38 mitogen-activated protein kinase (p38-MAPK) and nuclear factor kappa B (NF-kB) were performed on renal tissues. Results: The MDA levels were significantly lower in the quercetin-treated group than in the EG-treated group (p = 0.001). Although CAT levels were higher in the quercetin-treated group than the EG-administered group, they were not significantly different between these groups. The expression of p38 MAPK was significantly less in the quercetin-treated group than the EG group (p < 0.004). There was no statistically significant difference between the quercetin and EG groups in terms of NF-kB expression. Conclusions: We conclude that hyperoxaluria activated the signaling pathways, which facilitate the oxidative processes leading to oxalate stone formation in the kidneys. Our findings indicated that quercetin reduced damage due to hyperoxaluria. These results imply that quercetin can be considered a therapeutic agent for decreasing oxalate stone formation, especially in patients with recurrent stones due to hyperoxaluria.

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“…[22] Similarly, pentoxifylline also improves kidney function through attenuation of oxidative stress-induced AKI. [23]…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of berberine and pentoxifylline in attenuation of acute kidney injury

Al-Kuraishy

Al-Gareeb

Hussien

2019

Int J Crit Illn Inj Sci

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Objective: To evaluate the renoprotective effects of berberine and/or pentoxifylline in reduction of diclofenac-induced acute kidney injury (AKI) in rats. Material and Methods: Fifty male Sprague-Dawley rats were allocated into five groups, Group 1: Rats treated with distilled water plus normal saline for 12 days. Group 2: Rats treated with distilled water plus diclofenac for 12 days. Group 3: Rats treated with berberine plus diclofenac for 12 days. Group 4: Rats treated with pentoxifylline plus diclofenac for 12 days. Group 5: Rats treated with berberine + pentoxifylline plus diclofenac 15 mg/kg for 12 days. Blood urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecules (KIM-1), and cystatin-c were used to measure the severity of AKI. Results: Diclofenac led to significant AKI by significant elevation of blood urea, serum creatinine, KIM-1, and NGAL. Treatment with berberine showed no significant effect on all biomarkers level compared to diclofenac group except on serum KIM-1 level which also seen in the pentoxifylline group whereas combination of berberine and pentoxifylline led to more significant effect in the reduction of all renal biomarkers. Conclusion: Combination of berberine with pentoxifylline illustrated a synergistic effect in attenuation of diclofenac-induced AKI.

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Protective effect of pentoxifylline on oxidative renal cell injury associated with renal crystal formation in a hyperoxaluric rat model

Cited by 15 publications

References 50 publications

Metabolomic analysis reveals a protective effect of Fu-Fang-Jin-Qian-Chao herbal granules on oxalate-induced kidney injury

Metabolomic analysis reveals a protective effect of Fu-Fang-Jin-Qian-Chao herbal granules on oxalate-induced kidney injury

Protective Effects of Quercetin on Oxidative Stress-Induced Tubular Epithelial Damage in the Experimental Rat Hyperoxaluria Model

Synergistic effect of berberine and pentoxifylline in attenuation of acute kidney injury

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