Adelson M. Rodrigues

Nitric oxide (NO) is associated with gentamicin (GENTA) nephrotoxicity and the renal function recovery after suspension of GENTA treatment in rats.

GENTA nephrotoxicity is likely to be caused, among other factors, by an increase of vasoconstrictors or a decrease of vasodilators such as NO. Few days after discontinuing GENTA treatment, the renal function is recovered, but if risk factors like advanced age, previous renal dysfunction, simultaneous use of other nephrotoxic drugs or dehydration are present, severe and progressive renal disease occurs. The aim of this study was to evaluate the renal function in rats during GENTA treatment and after its suspension as well as its relationship with NO. Rats were treated with water (vehicle, CTL) or GENTA (100 mg/kg BW) intraperitonially during 10 days; both n=24. Twelve animals of each group were sacrificed after blood and 24 h urine were collected, and their kidneys were removed for histology. In another rats this procedure underwent after 20 or 30 days of GENTA suspension. GENTA treated group developed a marked decrease in renal function, characterized by an increased serum urea and decreased creatinine clearance; NO was increased in the serum and decreased in the urine; all P < 0.01 vs CTL. Acute tubular necrosis was confirmed in GENTA treated group. After GENTA suspension we observed a normalization of urea, creatinine clearance and serum and urinary NO; the histological lesions were also attenuated. We suggest that NO could play a role in GENTA induced nephrotoxicity and recovery. The understanding of this physiopathology could be an useful tool to prevent or blunt the nephrotoxicity progression, mainly when risk factors are present.

Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress

This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications.

Moderate aerobic exercise on the recovery phase of gentamicin-induced acute kidney injury in rats

Introduction: Acute kidney injury is a serious public health problem, especially in intensive care units, where patients may require dialysis support, resulting in 50% mortality. Aim: To evaluate the effects of moderate aerobic exercise on the recovery phase of acute kidney injury induced by gentamicin in rats. Main methods: Male adult Wistar rats were allocated into 4 groups: W10 + R30, G10 + R30, W10 + EX30 and G10 + EX30; W10 received water (gentamicin vehicle) and G10 received gentamicin for 10 days; R30 remained resting and EX30 made exercise for 30 days after gentamicin suspension. Training was performed on treadmill. Blood, 24 h urine and kidneys were collected for renal function and oxidative stress, antioxidant, TGF‐&bgr; and histological analysis. Key findings: Gentamicin treatment caused decreased renal function significant oxidative stress, reduced urinary nitric oxide and increased TGF‐&bgr;. G10 + R30 presented partial recovery of metabolic data, renal function and lipoperoxidation levels, although they were still altered compared to W10 + R30. Besides, we observed the presence of lymphomononuclear infiltrate in the kidneys of G10 + R30. G10 + EX30 vs G10 + R30 showed additional improvement of all the mentioned parameters, showing at histology, regeneration of the tubule epithelium. Significance: Our data suggest that moderate exercises could help in the recovery of metabolic parameters, renal function and structure on gentamicin‐induced AKI, perhaps due to restoration of redox balance. This could protect the kidneys from further insults like challenges with nephrotoxic drugs or the aging per se.