Anti-inflammatory and antioxidant activity of essential amino acid α-ketoacid analogues against renal ischemia-reperfusion damage in Wistar rats. / Actividad antiinflamatoria y antioxidante de los α-cetoanálogos de aminoácidos esenciales en un modelo de daño por isquemia-reperfusión en ratas Wistar

INTRODUCTION: Essential amino acid α-keto acid analogs are used in the treatment of chronic kidney disease to delay the symptoms of uremia. However, it is unknown whether essential amino acid α-keto acid analogs affect the oxidative stress and the inflammation in acute renal injury such as those produced by ischemia-reperfusion. OBJECTIVE: To evaluate the effect of essential amino acid α-keto acid analogs on renal ischemia-reperfusion injury in Wistar rats. MATERIALS AND METHODS: Rats were divided into 11 groups (n=6/group): Two groups received physiological saline with or without ischemia-reperfusion injury (45 min/24 h), six groups received essential amino acid α-keto acid analogs (400, 800, or 1,200 mg/kg/24 h/7d) with or without ischemia-reperfusion injury (essential amino acid α-keto acid analogs + ischemia-reperfusion), and two groups received allopurinol (50 mg/kg/24 h/7d) with or without ischemia-reperfusion injury. Biochemical markers included creatinine and blood urea nitrogen (BUN), proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), renal damage markers (cystatin C, KIM-1, and NGAL), and markers of oxidative stress such as malondialdehyde (MDA) and total antioxidant activity. RESULTS: The essential amino acid α-keto acid analog- and allopurinol-treated groups had lower levels of creatinine, BUN, renal damage markers, proinflammatory cytokines, and MDA than their corresponding ischemia-reperfusion groups. These changes were related to the essential amino acid α-keto acid analogs dosage. Total antioxidant activity was lower in essential amino acid α-keto acid analog- and allopurinol-treated groups than in the corresponding ischemia-reperfusion groups. CONCLUSIONS: This is a new report on the nephroprotective effects of essential amino acid α-keto acid analogs against ischemia-reperfusion injury. Essential amino acid α-keto acid analogs decreased the levels of biochemical markers, kidney injury markers, proinflammatory cytokines, and MDA while minimizing total antioxidant consumption.

Introducción. Los α-cetoanálogos de aminoácidos esenciales se utilizan en el tratamiento de la enfermedad renal crónica para retrasar los síntomas de la uremia. Sin embargo, se desconoce si los α-cetoanálogos de aminoácidos esenciales afectan el estrés oxidativo y la inflamación en la lesión renal aguda tal como en la producida por la isquemia-reperfusión. Objetivo. Evaluar el efecto de las α-cetoanálogos de aminoácidos esenciales sobre la lesión renal por isquemia-reperfusión en ratas Wistar. Materiales y métodos. Se emplearon 11 grupos de ratas (n=6): dos grupos recibieron solución salina fisiológica con lesión isquemia-reperfusión o sin ella (45 min/24 h), seis grupos recibieron α-cetoanálogos de aminoácidos esenciales (400, 800 o 1.200 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella (α-cetoanálogos de aminoácidos esenciales + isquemia-reperfusión), y dos grupos recibieron (50 mg/kg/24 h/7d) con lesión isquemia-reperfusión o sin ella. Los marcadores bioquímicos incluyeron creatinina y nitrógeno ureico en sangre (BUN), citocinas proinflamatorias (IL-1ß, IL-6 y TNF-α), marcadores de daño renal (cistatina C, KIM-1 y NGAL) y marcadores del estrés oxidativo como el malondialdehído (MDA) y la actividad antioxidante total. Resultados. Los grupos tratados con α-cetoanálogos de aminoácidos esenciales y alopurinol tuvieron niveles inferiores de creatinina, BUN, marcadores de daño renal, citocinas proinflamatorias, actividad antioxidante total y MDA que los grupos isquemia-reperfusión correspondientes. Estos cambios se asociaron con la dosis. La actividad antioxidante total fue menor en los grupos tratados con α-cetoanálogos de aminoácidos esenciales que en los grupos isquemia-reperfusión correspondientes. Conclusiones. Este es un nuevo informe de los efectos nefroprotectores de las α-cetoanálogos de aminoácidos esenciales contra la lesión isquemia-reperfusión. Los α-cetoanálogos de aminoácidos esenciales disminuyeron los niveles de los marcadores bioquímicos, de los de lesión renal, de las citocinas proinflamatorias y el MDA, a la vez que minimizaron el consumo total de antioxidantes.

Anti-inflammatory and nephroprotective activity of Juglans mollis against renal ischemia-reperfusion damage in a Wistar rat model.

BACKGROUND: Oxidative stress and the inflammatory process are involved in ischemia-reperfusion (I/R) injury. Juglans mollis has been reported as having antioxidant activity, which could attenuate the damage caused by I/R. We evaluated whether a methanolic extract of Juglans mollis (JM) exhibits nephroprotective activity in a Wistar rat model of I/R injury. METHODS: Four groups of six rats were used: Sham, I/R, JM, and JM + I/R. Two groups were dosed with JM (300 mg/kg) for 7 days before I/R. I/R injury was induced by clamping the renal hilums for 45 min and then reperfusing the kidneys for 15 h. Blood samples were taken to evaluate the levels of alanine aminotransferase (ALT), blood urea nitrogen, creatinine, superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α). RESULTS: The levels of creatinine, ALT, MDA, IL-1ß, IL-6, and TNF-α were lower in JM + I/R than in I/R rats, whereas SOD level only was higher in JM + I/R than in Sham rats. No biochemical or histological damage was observed in JM rats compared with Sham rats; however, less histological damage was observed in JM + I/R rats compared with I/R rats. CONCLUSIONS: To our knowledge, this is the first report of nephroprotective activity of J. mollis against damage induced by I/R. This activity may be related to decreased levels of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) and modulation of oxidative stress markers (SOD and MDA) observed in the present study.

Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury Induced by Ischemia-Reperfusion in Wistar Rats.

INTRODUCTION: Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. OBJECTIVE: To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. MATERIALS AND METHODS: Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. RESULTS: None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. CONCLUSIONS: S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R.

Hepatoprotective effect of commercial herbal extracts on carbon tetrachloride-induced liver damage in Wistar rats.

BACKGROUND: Various hepatoprotective herbal products from plants are available in Mexico, where up to 85% of patients with liver disease use some form of complementary and alternative medicine. However, only few studies have reported on the biological evaluation of these products. OBJECTIVE: Using a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, we evaluated the effects of commercial herbal extracts used most commonly in the metropolitan area of Monterrey, Mexico. MATERIALS AND METHODS: The commercial products were identified through surveys in public areas. The effect of these products given with or without CCl4 in rats was evaluated by measuring the serum concentrations of aspartate amino transferase (AST) and alanine amino transferase (ALT), and histopathological analysis. Legalon(®) was used as the standard drug. RESULTS: The most commonly used herbal products were Hepatisan(®) capsules, Boldo capsules, Hepavida(®) capsules, Boldo infusion, and milk thistle herbal supplement (80% silymarin). None of the products tested was hepatotoxic according to transaminase and histological analyses. AST and ALT activities were significantly lower in the Hepavida+CCl4-treated group as compared with the CCl4-only group. AST and ALT activities in the silymarin, Hepatisan, and Boldo tea groups were similar to those in the CCl4 group. The CCl4 group displayed submassive confluent necrosis and mixed inflammatory infiltration. Both the Hepatisan+CCl4 and Boldo tea+CCl4 groups exhibited ballooning degeneration, inflammatory infiltration, and lytic necrosis. The silymarin+CCl4 group exhibited microvesicular steatosis. The Hepavida+CCl4- and Legalon+CCL4-treated groups had lower percentages of necrotic cells as compared with the CCl4-treated group; this treatment was hepatoprotective against necrosis. CONCLUSION: Only Hepavida had a hepatoprotective effect.