Fernando Jaramillo-Juárez

INFLUENCE OF SEX DIFFERENCES ON THE RENAL SECRETION OF ORGANIC ANIONS

The kidney’s responsiveness to male sexual hormones has been often neglected. Renal secretion of organic anions is higher in male than in female individuals; as a consequence, most of the xenobiotics that are excreted from the organism through this pathway are eliminated more rapidly by males than by female animals. To gain further insight into this issue, we studied in vitro and in vivo characteristics of the transport of p-aminohippurate (PAH), a suitable marker for this system, in male and female rats, under different hormonal conditions. Kinetics of PAH showed a shorter elimination half-time in male than in female rats (t1/2el: male = 16.2 ± 2.1 min, female= 25.7 ± 4.5 min, P < 0.05). Castration of male rats increased t1/2el to a value similar to that of female rats (t1/2el: orchiectomized rat = 28.1 ± 7.1 min). Testosterone treatment of female rats increased the elimination rate to a value similar to that of male rats. In vitro PAH uptake by renal cortical slices from intact male rats was higher than...

Acidosis and weight loss are induced by cyclosporin A in uninephrectomized rats.

Abstract The effects of cyclosporin A (CyA, 50 mg/kg body weight) or its commercial vehicle (cremophor) on the acid-base regulation of uninephrectomized rats were assessed for 7 days and in non-nephrectomized rats for 15 days. CyA induced a marked systemic acidosis, accompanied by decreases in blood PCO2 and plasma bicarbonate. Untreated uninephrectomized rats did not show the acidosis. In CyA-treated rats the urine pH decreased (control 6.65±0.06 vs. CyA 6.18±0.08; P<0.01) as well as urinary bicarbonate (non-nephrectomized rats 7.50±1.88 mM vs. uninephrectomy plus CyA 0.75± 0.06 mM; P<0.01), suggesting partial renal compensation of systemic acidosis. Titratable acidity increased in CyA-treated rats (control 21.6±1.2 vs. CyA 63.3±12.0 µEq/l; P<0.001). Phosphate, glucose, and osmolar clearances were not significantly altered in non-nephrectomized rats treated with CyA for 15 days. There was a striking decrease in body weight in CyA-treated rats (control 274.0±3.8 vs. CyA 225.0±5.1 g; P<0.01), but compensatory growth of the remaining kidney was not prevented by this drug or by its vehicle. In summary, CyA induced a severe metabolic acidosis in uninephrectomized rats that was not compensated by the remaining kidney, in spite of the well-preserved compensatory weight gain of this organ. Loss of body weight was significant in CyA-treated animals.

Effects of aflatoxin B1 on the liver and kidney of broiler chickens during development

Aflatoxin B(1) (AFB(1)) negatively affects chicken (Gallus domesticus) growth. This effect is more severe during development. We studied the influence of age on the toxic effects of AFB(1) on plasma, renal and hepatic enzymes, under two protocols, in adult and in developing Arbor-Acres chickens. Protocol A: 100 male 4-week-old chickens (640 g), received AFB(1), 0.5, 1.0, or 2.0 microg/g of feed (daily p.o.), a fourth group received an aflatoxin-free diet. Five birds/group were slaughtered at 7, 14, 21 and 28 days of treatment. Body, hepatic and renal weights, succinate-dehydrogenase (SDH) and glutamate-dehydrogenase (GluDH) in plasma and liver were measured. Hepatic SDH and GluDH decreased (P<0.05). Protocol B: two groups of 24 male 1-week-old chickens (106 g) received either aflatoxin-free feed (n=24) or AFB(1) feed (2.0 microg/g). At days 7, 14, 21 and 28, the same parameters of Protocol A were measured. AFB(1) markedly reduced body weight gain (20-30%), plasma proteins, albumin, renal and hepatic protein content (P<0.05) and increased absolute and relative weights of the kidney (P<0.05). SDH and GluDH were reduced (P<0.05), while total renal gamma-glutamyltranspeptidase (GGT) increased (P<0.05). Results suggest that serum proteins, SDH and GluDH are sensitive early indicators of this toxicity that was more severe in developing chickens. Decrease in serum albumin might be used as an early and suitable indicator of the deleterious effect of this mycotoxin in developing chickens.

Urinary and proximal tubule acidification during reduction of renal blood flow in the rat.

1. The effects of reduction in renal blood flow (RBF) on urinary acidification and proximal tubule H+ ion secretion were studied after partial aortic clamping in rats. 2. Acute reduction of the renal perfusion pressure (from 109 +/‐ 3.88 to 77.4 +/‐ 1.05 mmHg) decreased both inulin and PAH (p‐aminohippurate) clearances to about one‐third of their control values. Absolute levels of urinary sodium excretion also decreased markedly, but fractional sodium excretion did not change significantly. 3. Urine pH and bicarbonate levels were not affected, but titratable acidity increased significantly from 0.12 +/‐ 0.011 to 0.25 +/‐ 0.042 muequiv min‐1 ml‐1 glomerular filtration rate (GFR). During aortic clamping, cortical PCO2 as determined by means of Severinghaus microelectrodes was reduced by a mean value of 7.0 +/‐ 1.5 mmHg. 4. Proximal tubule acidification kinetics were studied by stationary microperfusion techniques in which the time course of pH changes was monitored by pH microelectrodes. Steady‐state pH fell from a mean control value of 6.77 +/‐ 0.03 to 6.65 +/‐ 0.02, and stationary bicarbonate concentrations from 4.70 +/‐ 0.27 to 2.84 +/‐ 0.18 mM. Acidification half‐time decreased from 5.07 +/‐ 0.30 to 4.39 +/‐ 0.19 s, and net bicarbonate reabsorption increased from 1.63 +/‐ 0.14 to 1.99 +/‐ 0.12 nmol cm‐2 s‐1, these changes being statistically significant. 5. The experiments demonstrate that both overall acid excretion and proximal acid secretion are not compromised by a large decrease of RBF to about one‐third of the control value; titratable acid excretion and proximal net bicarbonate reabsorption were even moderately increased under these conditions.

Protective effect of Ginkgo biloba extract on liver damage by a single dose of CCl 4 in male rats

Functional and morphological alterations were generated by p.o. (per os) administration of a single oral dose of carbon tetrachloride (CCl4; 0.125 mL/kg b.w., equivalent to 293 mg/kg) to adult male Wistar rats. CCl4 significantly increased (p < 0.05) the serum activities of alanine aminotransferase (ALT; 7478 ± 1044%) and aspartate aminotransferase (AST; 6964 ± 833%), compared to control rats; CCl4 also significantly decreased serum concentration of albumin (23 ± 5.5%) and increased the concentration of malondialhdeyde (MDA) in liver (300 ± 33%). Furthermore, CCl 4 down-regulated the mRNA steady-state level of tumor necrosis factor a(TNF-a). CCl4 produced necrosis in the central lobe area, extended to the periphery, nuclear alterations (pycnosis, karyolysis and karyorrhexis), and cytoplasmic acidophilia. The pretreatment with 4 mg/kg (p.o.) of Ginkgo biloba extract (GbE), for 5 days, prevented most of the damage caused by CCl4: significantly decreased the serum activities of ALT and AST (54 and 65%, respectively), compared to CCl4-treated rats; GbE partially prevented the increase of liver MDA (55 ± 14%) and the decrease of albumin concentration to 12 ± 0.2%. This pretreatment prevented the down-regulation of TNF-a and up-regulated the interleukine 6 (IL-6) mRNA steady-state level. Moreover, the GbE reduced the amount of necrotic areas in the central lobe area, compared to CCl4-treated rats.

Effects of aflatoxin chronic intoxication in renal function of laying hens

Aflatoxins (AF) have a high impact in both human and animal health, causing significant economic losses in the poultry industry, especially by diminution of avian growth, feed efficiency, and product quality. Aflatoxins affect the whole organism, particularly liver and kidney. The objective of this study was to evaluate renal function alterations in laying hens during chronic AF ingestion. Randomly, 84 Leghorn Hy-Line laying hens (13 wk old) were assigned into 4 experimental groups (n = 21): 0.0, 0.5, 1.0, and 1.5 mg of AF/kg of feed. The AF (B(1), B(2), G(1), and G(2)) was obtained from 2 toxicogenic local strains of Aspergillus flavus grown in corn grains; the grain was sterilized, ground, and added to basal diets to achieve the selected AF concentrations. Hens ingested, during 17 and 42 wk, feed contaminated with AF. Data were analyzed in a 4 x 2 factorial arrangement. Hens were anesthetized, ureteral urine samples were collected, and arterial blood samples were taken. The renal functional tests were evaluated by spectrophotometric and flame photometric methods, including a) Na, K, Ca, and phosphate fractional excretions; b) renal hemodynamic studies, glomerular filtration rate and renal plasma flow by inulin and p-aminohippurate clearances, respectively; and c) identification of macroscopic and histopathologic lesions. The hens intoxicated at all levels of AF showed significant (P < 0.05) increases in Ca, Na, and phosphate fraction excretions. Sodium and phosphates were excreted in a pattern of response time-dose. However, glomerular filtration rate exhibited a significant reduction (P < 0.05). The K fractional excretion and renal plasma flow remained unchanged. These results suggest that AF chronic ingestion affects renal functions of laying hens and induces Ca(++), (-3)PO(4), and Na(+) losses, which are of great concern to the poultry industry.

Beneficial effects of quercetin on oxidative stress in liver and kidney induced by titanium dioxide (TiO2) nanoparticles in rats

Abstract TiO2 nanoparticles used as vectors for the delivery of drugs have shown greater effectiveness. However, TiO2 nanoparticles can cause oxidative stress in liver and kidney, so we analyzed if a previous or simultaneous quercetin treatment could counteract this in rats. Five groups of male Wistar rats (200–250 g) were included: (1) healthy controls, (2) TiO2 group, (3) quercetin group, (4) preventive group: quercetin for 5 days prior to exposure of TiO2, and (5) therapeutic group: TiO2 (5 mg/kg, i.v.) plus quercetin single dose for 5 days (5 mg/kg/day, i.p.). Hepatic and renal function tests were made. Five animals from each group were sacrificed (0, 14 and 28 days), and liver and kidney tissue were obtained. Malondialdehyde (MDA), reduced/oxidized glutathione, and activity of glutathione peroxidase/reductase were measured, as well as the level of gene expression by q-PCR. There were no significant changes in serum ALT and AST activities. More damage was observed at 14 versus 28 days, because TiO2 was excreted in urine. Quercetin indeed showed a renal protective effect by increasing glutathione reductase and peroxidase levels and reducing MDA levels. On the other hand, TiO2 liver damage was less pronounced with quercetin as therapeutic treatment. TiO2 induces significantly the glutathione reductase expression and it can be down-regulated by quercetin. Biochemical tests in serum and urine showed a better effect of quercetin administered in the therapeutic group. Care should be taken with the dose and time of administration of quercetin, because this antioxidant could also have a pro-oxidant effect.

Renal failure during acute toxicity produced by tullidora ingestion (Karwinskia humboldtiana).

1. Acute effects of Karwinskia humboldtiana (Kh) were studied in some renal functions and structural patterns of renal tissue. 2. Haemodynamic changes were observed with decrements of the glomerular filtration rate, renal plasma flow and filtration fraction during acute intoxication. 3. A marked increment in the fractional excretion of sodium was observed in the rats treated with tullidora fruits (Kh). 4. Cloudy swelling and hydropic degeneration was seen 72 hr after intoxication, mainly in the proximal convoluted tubules.

Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-l-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800 mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20 mmol/L APAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.

The flavonoid quercetin protects and prevents against potassium dichromate-induced systemic peroxidation of lipids and diminution in renal clearance of para-aminohippuric acid and inulin in the rat.

It is well known that exposure to chromium (Cr) can lead to nephrotoxicity. Quercetin is a flavonoid of interest because of its proposed health-promoting effects. The aim of this work was to elucidate the role of quercetin against the nephrotoxicity caused by Cr in rats. Quercetin may have positive effects in combating, or helping to prevent, nephrotoxicity. It was observed that a single dose of potassium dichromate resulted in both an increase of systemic peroxidation of lipids and a decrease of the renal clearance of para-aminohippuric acid and inulin. Our results show that treatment with quercetin protected and prevented against these damaging effects.