Previous exposure to cigarette smoke aggravates experimental cyclosporine-induced nephrotoxicity.

BACKGROUND/AIMS: The effects of cigarette smoke (CS) on cyclosporine (CsA)-induced nephrotoxicity are poorly studied. This study aims to assess the effects of previous exposure to CS on CsA nephrotoxicity. METHODS: Rats were either exposed to CS or sham (S) procedures for 10 min twice a day for 20 weeks. From the 16th to the 20th week, they received a low-salt diet. Beginning with the 17th week, they were given 2.5 mg/day CsA or vehicle (VH) for 3 weeks. The final groups were VH/CS, CsA/CS, VH/S, and CsA/S. On day 141, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), tubulointerstitial fibrosis, and CsA blood levels were measured and immunohistochemistry was analyzed for renal α-smooth muscle actin (SMA), nitrotyrosine, and vimentin. RESULTS: CsA decrease in GFR was enhanced by CS exposure. CsA associated with CS induced higher periglomerular α-SMA and renal nitrotyrosine expression. CsA decreased RBF, but increased RVR, tubulointerstitial fibrosis, and α-SMA and renal vimentin expression. These changes and the CsA blood levels were not affected by CS exposure. CONCLUSION: CS aggravated the CsA-induced impairment of GFR and CS associated with CsA caused the development of periglomerular structural lesions and oxidative stress in a rat model of CsA nephrotoxicity.

Ga-67 scintigraphy in the differential diagnosis between acute interstitial nephritis and acute tubular necrosis: an experimental study.

BACKGROUND: The differentiation between acute interstitial nephritis (AIN) and acute tubular necrosis (ATN) is crucial in patients with acute kidney injury. Gallium-67 citrate (Ga-67) has been used clinically in the differential diagnosis between these entities, but its efficacy is disputed. The aim of this study was to evaluate Ga-67 scintigraphy efficacy in the differentiation between experimental models of drug-induced AIN and ATN. METHODS: Animals were divided into three groups: AIN (n = 8), ATN (n = 8) and control (NL, n = 10). The AIN group received intraperitoneal puromycin aminonucleoside (single dose, 150 mg/kg). The ATN group received a single intraperitoneal injection of cisplatin (6 mg/kg). The NL group did not receive active drugs. All of the animals were submitted to Ga-67 scintigraphy, serum creatinine (Cr) and urinary osmolality assessment, and blinded renal histology evaluation. RESULTS: Renal Ga-67 uptake was strikingly more intense in the AIN group when compared to the ATN (P < 0.0001) and NL (P < 0.001) groups. The ATN group had increased Cr when compared to the NL group (P < 0.001) and lower urinary osmolality vs the NL (P < 0.001) and AIN (P < 0.01) groups. Renal histology showed severe acute tubular injury in the ATN group and intense interstitial inflammation in the AIN group, and was normal in control animals. CONCLUSION: Ga-67 scintigraphy was extremely effective in the differentiation between experimental drug-induced ATN and AIN.

The effects of so-called 'forbidden acupuncture points' on pregnancy outcome in wistar rats.

BACKGROUND: This study sought to determine if acupuncture in LI4 and SP6, or in sacral points could harm the pregnancy outcome in Wistar rats as is believed according to traditional knowledge. METHODS: 48 pregnant Wistar rats were randomly divided into 4 groups: total control where the rats were left in cages without manipulation; anesthetized control where the rats were manipulated and anesthetized but did not received electroacupuncture; peripheral points and sacral points were the rats were anesthetized and received 4 acupuncture points - LI4-SP6 and BL27-28, respectively. The primary end point was embryonic loss after implantation, defined as (number of implantations - number of embryos in development) × 100 / number of implantations. Other evaluated parameters were fetal death, abortions, number of fetuses, and resorptions, resorption index (number of resorptions / total of implantations), maternal weight gain, and fetal weight. RESULTS: There were no differences in embryonic loss after implantation (p = 0.45), fetal death (p = 1), abortions (p = 1), number of fetuses (p = 0.79), resorptions (p = 0.3), and resorption index (p = 0.45). There were differences in maternal weight gain and fetal weight, but they seemed unrelated to the treatment. CONCLUSIONS: We found no evidence that acupuncture in LI4-SP6 and sacral points could be harmful to the pregnancy outcome in Wistar rats.

Macrophage depletion attenuates chronic cyclosporine A nephrotoxicity.

BACKGROUND: Cyclosporine A (CsA)-induced chronic nephrotoxicity is characterized by renal dysfunction and interstitial fibrosis. Early and progressive renal macrophage influx, correlating with latter interstitial fibrotic areas, has been associated with CsA treatment. This study investigated the role of macrophages, the nitric oxide (NO) pathway, and the oxidative stress on chronic CsA nephrotoxicity. METHODS: The macrophages were depleted by clodronate liposomes. Animals were distributed into four groups: vehicle (olive oil for 21 days), CsA 7.5 mg/kg per day (21 days), CsA plus clodronate (5 mg/mL intraperitoneally on days -4, 1, 4, 11, and 18 of CsA treatment), or vehicle plus clodronate. On day 22, glomerular filtration rate, renal blood flow, renal tubulointerstitial fibrosis, CsA blood levels, serum malondialdehyde and renal tissue immunohistochemistry for macrophages, inducible NO synthase, transforming growth factor-beta, nuclear factor-kbeta, alpha-smooth muscle actin, vimentin, and nitrotyrosine were assessed. RESULTS: CsA-induced increase in the macrophage was prevented by clodronate. Macrophage depletion attenuated the reductions in the glomerular filtration rate and renal blood flow, the development of tubulointerstitial fibrosis, malondialdehyde increase and increases in nuclear factor-kbeta, transforming growth factor-beta, vimentin, inducible NO synthase, and nitrotyrosine expression provoked by CsA. Clodronate did not affect alpha-smooth muscle actin expression and CsA blood levels. CONCLUSIONS: Renal macrophage influx plays an important role in CsA-induced chronic nephrotoxicity. The NO pathway and oxidative stress are likely mechanisms involved in the genesis of this form of renal injury.