The Effect of High Dosage of Codeine-Containing Cough Syrup on Renal Function on Albino Rats

Codeine-containing cough syrup (CCS) is one of the most abused drugs in the world especially among the youths. However, there is need to study the nephrotoxic effect associated with oral administration of the drug and to ascertain its effect on the kidney. Consequently, understanding the renal abnormalities in chronic use of CCS will be crucial for effective development of interventions. This study assessed the nephrotoxic effect associated with oral administration of codeine-containing cough syrup (Tutolin with Codeine) in albino rats, using the level of creatinine, urea, sodium, potassium and chloride ions as biomarker in the serum of albino rats. The rats were administered orally with Tutolin and Codeine at a dose of 80mg/kg, 160mg/kg, 240 mg/kg and 320mg/kg body weight. After three weeks of oral administration of the syrup to all the groups, there was no difference (P> 0.05) in the levels of sodium ion, chloride ion and creatinine among all the study groups and levels of urea and potassium ion in the group administered with 80 mg/kg, 160 mg/kg and 240 mg/kg body weight of tutolin with codeine compared with the control. After three weeks of oral administration of 80 mg/kg, 160 mg/kg, 240 mg/kg and 320 mg/kg body weight tutolin with codeine cough syrup, urea and potassium ion concentrations were higher (p<0.05) in group given 320mg/kg body weight of tutolin with codeine cough syrup compared with the control. This suggests that at higher doses, tutolin with codeine containing cough syrup may have effect on the kidney.

Nicorandil prevents the nephrotoxic effect of cyclosporine-A in albino rats through modulation of HIF-1α/VEGF /eNOS signaling

Despite cyclosporine-A (CsA) is a widely used immunosuppressive drug; its nephrotoxic effect puts a limitation for chronic administration. Herein we tried to investigate its renal effect on endothelial dysfunction targeting the hypoxia-inducible factor (HIF-1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) pathway and the possible modulation by nicorandil. Eight groups of adult male Wistar rats were included; 1: control, 2: vehicle group (received oil), 3: glibebclamide 5mg/kg/day/orally was administered. 4: group received nicorandil 10mg/kg/day/orally. 5: group received cyclosporine 25mg/kg/day/orally. 6: combined cyclosporine and nicorandil, 7: glibenclamide was added to cyclosporine, and 8: group received both cyclosporine and nicorandil combined with glibenclamid. The treatment continued for 6 weeks. Combined nicorandil with cyclosporine improved renal function deterioration initiated by cyclosporine. Cyclosporine decreased the renal expression levels (P<0.001) of HIF-1α, eNOS, and VEGF inducing endothelial dysfunction and the triggered inflammation, and upregulated the pro-fibrotic marker transforming growth factor (TGF-β). Nicorandil fixed the disturbed HIF-1α/VEGF/eNOS signaling. Nicorandil corrected the renal functions confirmed by improved the histological glomerular tuft retraction that was obvious in the cyclosporine group, without significant influence by glibenclamid. Proper protection from CsA-induced nephrotoxicity was achieved by nicorandil. Nicorandil reversed the disturbed HIF-1α/VEGF/eNOS pathway created by cyclosporine.

Comparative histology of wild-type and p53-deficient medaka (Oryzias latipes): nephrotoxic effect of ultraviolet A radiation

Ultraviolet radiation is an ecological factor that directly affects terrestrial organisms through suppression of immunity or damage to internal organs.

Ethyl silicate Documentation of proposed values of occupational exposure limits (OELs)

Ethyl silicate is a colorless liquid with a slightly perceptible odor. This compound finds numerous applications in many industrial branches, e.g., paint and lacquer, chemical (in chemical coatings which has a contact with food), pharmaceutical, semiconductor and in nanotechnology. It is also used as an agent to harden natural stone, terra-cotta, artificial marble, frescoes and clay and in pro-duction of waterproof and acidproof mortar and cements. According to the State Sanitary Inspection data, in Poland in 2007, 2010 and 2013, there were no workers Ortokrzemian tetraetylu. Dokumentacja proponowanych dopuszczalnych wielkości narażenia zawodowego 23 exposed to ethyl silicate at levels exceeding maxi-mum allowable concentration (MAC) of 80 mg/m3. Ethyl silicate is well absorbed via respiratory and alimentary tracts, but its absorption through the skin is rather poor. In workers exposed to ethyl sil-icate, irritating properties to eye and nasal mucosa have been observed. Data on chronic ethyl silicate effects in humans are not available in the literature. In laboratory animals, ethyl silicate acute toxicity expressed in median lethal doses is relatively low. Ethyl silicate shows a mild irritating effect on rab-bit’s eyes, it does not cause dermal irritation or al-lergic effects. There are no data on ethyl silicate chronic toxicity. Short-term and subchronic studies performed on mice and rats exposed to ethyl sili-cate through inhalation and after its administration in other ways showed except for necrotic lesions in the olfactory epithelium of nasal cavity (in mice), changes in the liver (in rats) and kidneys. The latter comprised interstitial inflammation and necrotic lesions in renal tubules. Short-term exposure of rats to high ethyl silicate concentrations induced its toxic effect also on lungs. Ethyl silicate mutagenic effect has not been re-vealed in Ames tests. On the basis of few data, it has been proved that this compound did not cause reproductive and developmental toxicity. This compound has not been categorized by the Inter-national Agency for Research on Cancer (IARC) with respect to its potential carcinogenic risk. The presented evidence shows that the major toxic effect of ethyl silicate at high concentrations (over 2000 mg/m3) is eye and nasal mucosa irritation in humans, whereas the nephrotoxic effect and dam-age to the olfactory epithelium of nasal cavity are observed in laboratory animals. On the basis of the nephrotoxic effect of ethyl sili-cate, its maximum allowable concentration (MAC) was calculated. The results of two independent in-halation experiments in mice were used to deter-mine NOAEL value. Inhalation exposure of mice to ethyl silicate at concentration of 430 mg/m3 (50 ppm) for 90 days or 2 and 4 weeks did not cause nephrotoxic effects. This compound at higher con-centrations caused nephrotoxicity. Exposure to concentration of 760 mg/m3 (88 ppm) caused sig-nificant decrease in kidney weight, and after expo-sure to concentration of 865 mg/m3 (100 ppm) in 20% of animals interstitial inflammation of kidney tubules have been observed. The authors of the documentation proposed to adopt a concentration of 430 mg/m3 as NOAEC value of ethyl silicate for the nephrotoxic effects observed in mice. After adopting relevant uncertainty coefficients (total value, 8) the calculated MAC value for ethyl silicate is 54 mg/m3. Taking into consideration the fact that in 2008 SCOEL proposed a concentration of 44 mg/m3 as 8-h TWA for ethyl silicate, which was based on the same effects (nephrotoxicity) and NOAEC value adopted from the same experiments, it was pro-posed to assume a concentration of 44 mg/m3 as MAC value of ethyl silicate. This substance is in-cluded in the directive establishing the IV list of in-dicative occupational exposure limit values with-out establishing a short-term STEL value. The proposed MAC value for ethyl silicate should protect workers against systemic effect and poten-tial irritating effect. There are no reasons for adopt-ing STEL and BEI values for this compound.