Chronic kidney disease (CKD) is known to involve inflammation, oxidative stress and apoptosis. Here, we investigated the impact of curcumin (diferuloyl methane, a phenolic turmeric pigment), which has strong antioxidant, anti-inflammatory and anti-apoptotic activities on kidney structure and function in rats with adenine-induced CKD. Rats were treated for 5 weeks with adenine to induce CKD-like renal damage and combined with three doses of curcumin. Markers of kidney function and oxidative stress were quantified in plasma, urine, renal homogenates and on kidney tissue. Curcumin was found to significantly abate adenine-induced toxic effects such as reduced creatinine clearance, elevated neutrophil gelatinase-associated lipocalin levels and raised urinary N-acetyl-b-D-glucosaminidase activities. Curcumin markedly reduced renal morphological damage and histopathological markers of inflammation, fibrosis and apoptosis. Curcumin further reduced adenine-induced hypertension, urinary albumin, the inflammatory cytokines IL-1b, IL-6 and TNF-a, cystatin C and adiponectin. It restored plasma sclerostin concentrations and lowered oxidative stress in renal homogenates. In animals treated with the two higher curcumin concentrations, alone or in combination with adenine, an increased expression of the antioxidative transcription factor Nrf2 was found as well as up-regulation of the activity of its direct target glutathione reductase, and of an indirect target, the glutathione level. In conclusion, curcumin exhibits salutary effects against adenine-induced CKD in rats by reducing inflammation and oxidative stress via up-regulation of the transcription factor Nrf2.Chronic kidney disease (CKD) is a major and growing public health problem in both developed [1] and developing countries [2]. CKD is considered a key determinant of the poor health outcome of major non-communicable diseases [3] because of the high prevalence of morbidity and mortality associated with it, mainly due to cardiovascular dysfunction. Till now, there is no drug to improve kidney function in patients with CKD. The current therapeutic approaches to slow down its progression are limited to normalization of insulin, glucose and blood pressure [4]. Therefore, the development of novel therapies to either slow or reverse the deterioration in kidney function is highly needed. In particular, interesting for this are natural products with proven safety profiles.The pathophysiological basis of CKD and its complications include inflammation, oxidative stress and apoptosis [5]. These features consistently occur in human beings and animals. They are also major mediators of the disease, exerting similar effects in chronic renal failure models in rats [6,7]. Patients and laboratory animals with CKD have high plasma concentrations of inflammatory mediators (such as C-reactive protein, tumour necrosis factor and other cytokines) and several markers of nitrosative and oxidative stress [8,9]. Turmeric (Curcuma longa) is a popular Asian spice that has been utilized for...

Background/Aims: The effect of treatment with gum acacia (GA), a prebiotic shown previously to ameliorate chronic kidney disease (CKD), in diabetic and non – diabetic rats with adenine – induced CKD has been investigated using several conventional and novel physiological, biochemical, and histopathological parameters. Methods: Diabetes mellitus was induced in rats by a single injection of streptozotocin (STZ). Diabetic and non – diabetic rats were randomly divided into several groups, and given either normal food or food mixed with adenine (0.25% w/w, for five weeks) to induce CKD. Some of these groups were also concomitantly treated orally with GA in the drinking water (15% w/w). Results: Rats fed adenine alone exhibited physiological (decreased body weight, increased food and water intake and urine output), biochemical (increase in urinary albumin/creatinine ratio, plasma urea and, creatinine, indoxyl sulfate and phosphorus), inflammatory biomarkers (increased in neutrophil gelatinase-associated lipocalin, transforming growth factor beta -1, tumor necrosis factor alpha, adiponectin, cystatin C and interleukin-1β), oxidative biomarkers (8-isoprostane, 8 -hydroxy -2-deoxy guanosine), nitrosative stress biomarkers (nitrite and nitrate) and histopathological (increase in tubular necrosis and fibrosis) signs of CKD. STZ - induced diabetes alone worsened most of the renal function tests measured. Administration of adenine in STZ – diabetic rats further worsened the renal damage induced by adenine alone. GA significantly ameliorated the renal actions of adenine and STZ, given either singly or in combination, especially with regards to the histopathological damage. Conclusion: GA is a useful dietary agent in attenuating the progression of CKD in rats with streptozotocin-induced diabetes.

The erectile dysfunction drug sildenafil has cardiopulmonary protective actions, and a nephroprotective action in cisplatin and ischemia-reperfusion-induced acute kidney injury. Here, we assessed its possible ameliorative action in a model of chronic kidney disease (CKD) using adenine feeding. Eight groups of rats were treated with saline (controls), adenine (0.25% w/w in feed daily for 5 weeks), and oral sildenafil (0.1, 0.5 or 2.5 mg/kg), either alone, or concomitantly with adenine. Urine was collected 24 h after the end of the treatments from all rats and blood pressure measured, followed by collection of blood and kidneys for the measurement of several functional, biochemical and histopathological parameters. Adenine treatment reduced body weight, creatinine renal clearance, and increased water intake and urine output, as well as the plasma concentrations of urea and creatinine, neutrophil gelatinase-associated lipocalin, and N-acetyl-β-D-glucosaminidase activity, and albumin in urine. Adenine also increased the concentrations of the uremic toxins indoxyl sulfate, uric acid and phosphate, and a number of proteins and inflammatory cytokines, and decreased that of several anti - oxidant indices. Renal histopathological markers of damage (inflammation and fibrosis) were significantly increased by adenine. Sildenafil, given simultaneously with adenine, induced a dose - dependent improvements in most of the above parameters, suggesting its possible use as adjunct treatment for CKD in humans.

Patients with chronic kidney disease (CKD) have been reported to benefit from different types of exercises. It has also been shown that the ACE inhibitor lisinopril, and the natural product curcumin are also beneficial in different models of CKD in rats. We assessed the influence of moderate swimming exercise (SE) on rats with adenine-induced CKD, and tested the possible effects of lisinopril and/or curcumin thereon using several physiological, biochemical, histopathological and immunohistochemical parameters. Rats (either sedentary or subjected to SE) were randomly divided into several groups, and given for five weeks either normal food or food mixed with adenine (0.25% w/w) to induce CKD. Some of these groups were also concomitantly treated orally with curcumin (75 mg/kg), or lisinopril (10 mg/kg) and were subjected to moderate SE (45 min/day three days each week). Rats fed adenine showed the typical biochemical, histopathological signs of CKD such as elevations in blood pressure, urinary albumin / creatinine ratio, and plasma urea, creatinine, indoxyl sulfate and phosphorus. SE, curcumin or lisinopril, given singly, significantly ameliorated all the adenine-induced actions. Administering curcumin or lisinopril with SE improved the histopathology of the kidneys, a salutary effect not seen with SE alone. Combining SE to the nephroprotective agents’ curcumin or lisinopril might offer additional nephroprotection.

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Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that is currently available for the management of type 2 diabetes mellitus. The present study investigated the effect of canagliflozin on cisplatin (CP)-induced nephrotoxicity in mice. The animals were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (20 mg/kg) on day 7, respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (20 mg/kg) on day 7 and canagliflozin (10 mg/kg/day) and (30 mg/kg/day), for 10 days, respectively. At day 11, animals were anesthetized and blood collected and kidneys were removed. CP significantly increased the plasma urea, creatinine, cystatin C, and clusterin concentrations and neutrophil gelatinase-associated lipocalin (NGAL) activity. In addition, CP increased urinary albumin/creatinine ratio, N-acetyl-β-D-glucosaminidase (NAG) activity, and liver-type fatty acid-binding protein (L-FABP) concentrations and reduced creatinine clearance. CP also significantly increased the plasma concentration of inflammatory cytokines [plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β)] and significantly reduced antioxidant indices [catalase, glutathione reductase (GR), and superoxide dismutase (SOD)]. Histopathologically, CP caused a remarkable renal damage compared with control. Canagliflozin significantly ameliorated CP-induced biochemical and histopathological changes. The protective effect of canagliflozin is most likely due to anti-inflammatory and antioxidant effects. Our results show that administration of canagliflozin reversed the biochemical and histopathological indices of CP-induced nephrotoxicity in mice.

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