Nanomicelle curcumin-induced testicular toxicity: Implications for altered mitochondrial biogenesis and mitophagy following redox imbalance.

The purpose of this study was to examine the effects of nano-micelle curcumin (NMC)-induced redox imbalance on mitochondrial biogenesis and mitophagy. For this purpose, 24 mature male Wistar rats were divided into control and NMC-received groups (7.5, 15, and 30 mg/kg) groups. After 48 days, the Nrf1, Nrf2, and SOD (Cu/Zn) expression levels, as well as GSH/GSSG, NADP+ /NADPH relative balances (elements involved in redox homeostasis) were analyzed. Moreover, to explore the effect of NMC on mitochondrial biogenesis, the expression levels of Mfn1, Mfn2, OPA1, Fis1, and Drp1 were investigated. Finally, the expression levels of Parkin/PARK and PINK (genes involved in mitochondrial quality control), as well as LC3-I/II (mitophagy marker), were analyzed. Observations showed that NMC, dose-dependently, altered GSH/GSSG, NADP+ /NADPH relative balances, suppressed SOD expression and diminished its biochemical level, and repressed Nrf1 and Nrf2 expression levels. Moreover, it could change the Mfn1, Mfn2, OPA1, Fis1, and Drp1 expression pattern and stimulate the Parkin/PARK and PINK as well as LC3-I/II expression levels, dose-dependently. In conclusion, chronic and high-dose NMC is able to suppress the redox capacity by down-regulating the Nrf1 and Nrf2 expression. Finally, at high-dose levels, it is able to trigger mitophagy signaling in the testicles.

Determination of oxidative stress and effect of erdosteine on rhinitis medicamentosa in a rat model.

We aimed to determine the presence of oxidative stress in rhinitis medicamentosa (RM) and to evaluate the effect of erdosteine (ED) on mucosal changes in a rat model. Twenty-four male rats were used in this experimental study. Three groups were created. Group 1 (n=8) was the control group. Two puffs of 0.05% oxymetazolin were sprayed into the nasal cavities of the remaining rats (n=16) three times daily for eight weeks. One of these 16 rats was scarified at the end of the eight weeks and examined to confirm the presence of RM. Seven of the remaining 16 rats were killed, and venous blood samples were taken (Group 2). Group 3 (n=8) received 10mg/kg of an ED suspension orally for seven days. All rats were put on formalin for light microscopy. The total antioxidant status (TAS) was similar in all groups (p=0.073). The total oxidative status (TOS) of the RM group was significantly higher than that of the control group and RM+ED group (Group 3) (p=0.003 and p=0.011, respectively). The pathological recovery of the nasal mucosa of the rats was similar in the RM+ED and control groups. The TOS was high in this RM rat model, and oxidative stress was associated with RM. ED significantly ameliorated nasal mucosal changes induced by RM, suggesting that oxidative stress may play an important role in the pathophysiology of this condition.

Lipoprotein subfraction profile and HDL-associated enzymes in sickle cell disease patients.

Although hypocholesterolemia is a reported finding in sickle cell disease (SCD), low-density lipoprotein (LDL)/high-density lipoprotein (HDL) subfractions and HDL-associated enzymes have not been determined in SCD patients. Blood was collected from 38 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients who had not received blood transfusions in the last 3 months. Serum lipids were measured by automated analyzer while LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Serum levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were significantly decreased, while TG levels were significantly increased in SCD patients compared to controls. A significant decrease in intermediate-density lipoprotein (IDL)-C, IDL-B, IDL-A and LDL-1 fractions were seen in SCD patients, while no significant difference was observed in small dense LDL particles. A significant decrease was seen in HDL-large, HDL-intermediate and HDL-small fractions in SCD patients versus controls. Levels of LCAT and ApoA-1 protein measured in SCD patients were significantly lower while no significant difference was observed in CETP and ApoB protein levels compared to controls. The reduction observed in LDL- and HDL-C in SCD patients was reflected as significantly decreased IDL, LDL-1 and HDL-subfractions. Decreased HDL subfractions may possibly lead to the reduced ApoA-1 and LCAT protein levels observed in SCD patients.

Antioxidative and anti-inflammatory effect of thymoquinone in an acute Pseudomonas prostatitis rat model.

INTRODUCTION: The aim of this study is to investigate the potential antioxidant and anti-inflammatory effects of thymoquinone (TQ) to improve acute bacterial prostatitis (ABP) induced by Pseudomonas aeruginosa. MATERIAL AND METHODS: A total of 42 male Wistar albino rats were divided into 7 groups as follows: control, ABP (24, 48, and 72 h), and TQ-ABP (24, 48, and 72 h). The prostate tissue samples were assayed for prostate tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities. Sections were examined for characteristic histological changes, and a histological scoring system was used. RESULTS: When the ABP groups given TQ (24, 48, and 72 h) were compared to the ABP groups not given TQ, the levels of MDA and NO and the GPX activity were found to be significantly lower in the groups given TQ. Concerning SOD values, the TQ-ABP-72 group was lower in comparison with the ABP-72 and control groups, but statistically higher than the TQ-ABP-48 group (p < 0.05). Concerning CAT activity, only the TQ-ABP-72 and ABP-72 groups had a significant difference with the control group. TQ improved prostate histology significantly only in the TQ-ABP-24 group compared to the ABP-24 group (p < 0.001). CONCLUSION: Our study demonstrated for the first time that ABP induced by P. aeruginosa had an oxidative effect on prostate tissue and could regress following TQ administration as shown with the biochemical and histological findings.

Thyroid Doppler indices in patients with sickle cell disease.

OBJECTIVE: To evaluate the intrathyroidal hemodynamic changes and thyroidal volume in sickle cell disease (SCD) patients. METHODS: Thirty-two patients with homozygous SCD and 32 control subjects were examined with color Doppler ultrasonography. None of the patients and control subjects had clinical or laboratory evidence of thyroid disease. RESULTS: SCD patients had significantly higher resistance index (RI) and pulsatility index (PI) values and lower thyroid volume compared with control group. CONCLUSION: Increased intrathyroidal RI and PI and decreased thyroid volume may be due to impaired thyroidal microcirculation. Further and follow-up studies are needed to explain the relationship between Doppler parameters and thyroid functions.

Protective effects of thymoquinone against methotrexate-induced testicular injury.

Thymoquinone is the major active component derived from Nigella sativa. Methotrexate is a folic acid antagonist widely used in clinic. Aim of this study was to investigate the possible protective role of thymoquinone on testicular toxicity of methotrexate. Experiments were performed on male C57BL/6 mice (6 weeks old, 20 ± 2 g). The animals were divided into four groups with six mice in each group. Equivalent volumes of saline were injected intraperitoneally (i.p.) in the control group. In the thymoquinone group, mice received thymoquinone i.p. with a dose of 10 mg/kg/day for 4 days. Mice in the methotrexate group received single dose of methotrexate i.p., with a dose of 20 mg/kg. Finally, in the methotrexate plus thymoquinone group, in the first and the following 3 days after methotrexate administration, thymoquinone was injected with a dose of 10 mg/kg/day, i.p. At the end of the experiment, the left testis was quickly removed and divided into two parts for histological examination and biochemical analysis. Methotrexate alone increased total antioxidant capacity and myeloperoxidase activity compared to the controls. Thymoquinone treatment decreased total antioxidant capacity and prevented the increase in the myeloperoxidase activity. Light microscopy showed in mice that receiving methotrexate resulted in interstitial space dilatation, edema, severe disruption of the seminiferous epithelium and reduced diameter of the seminiferous tubules. Administration of thymoquinone reversed histological changes of methotrexate significantly. We suggest that thymoquinone use may decrease the destructive effects of methotrexate on testicular tissue of patients using this agent.

The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis.

We aimed to establish the relationship between serum vitamin D levels and disease activity and health status in rheumatoid arthritis. Sixty-five patients with RA fulfilling ACR criteria for the classification of rheumatoid arthritis and forty healthy controls were included in this study. Disease activity was assessed according to the Disease Activity Score including 28 joint counts. C-reactive protein (CRP, mg/dl) was determined by the nephelometric method. Erythrocyte sedimentation rate (ESR, mm/h) was determined by the Westergren method. Rheumatoid factor (RF, IU/ml) was also determined by the nephelometric method, and RF > 20 IU/ml was defined as positive. 25-OH Vitamin D EIA Kit was used to measure serum 25-OH Vitamin D levels. We found that the mean of the 25-OH D vitamin levels of the patients with RA was not different than that of controls (P = 0.936). We divided patients with RA into three groups according to DAS28 as low activity group (group 1, n = 25), moderate activity group (group 2, n = 25), and high activity group (group 3, n = 15). 25-OH vitamin D levels of the patients in the high activity group (group 3) were found to be the lowest (P < 0.001), and the patients with moderate disease activity had lower levels than those in the mild group (P = 0.033). Serum 25-OH vitamin D levels were significantly negatively correlated with DAS28, CRP, and HAQ (respectively, r = -0.431, P = 0.000, r = -0.276, P = 0.026, and r = -0.267, P = 0.031). Serum vitamin D levels in patients with RA were similar those in the healthy controls, while it significantly decreases in accordance with the disease activity and decreasing functional capacity.

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

Effects of caffeic acid phenethyl ester on isoproterenol-induced myocardial infarction in rats.

OBJECTIVE: Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti-inflammatory, antitumor and antioxidant activities and attenuates inflammation and lipid peroxidation induced by ischemia-reperfusion injury. The purpose of the present study was to investigate the effects of CAPE on isoproterenol (ISO) -induced myocardial infarction. METHODS: A randomized controlled experimental design was used in this study. Rats were divided into four groups and treated with saline, CAPE, ISO and ISO+CAPE. Rats were treated with CAPE (10 micromol kg/day i.p.) or saline starting 3 days before injecting ISO (150 mg /kg s.c., 24 hours). Seven days later, rats were sacrificed and the hearts were excised for biochemical analyses and microscopic examination. One-way ANOVA test with post hoc multiple comparisons using LSD method were used for statistical analysis of the data. RESULTS: The administration of ISO alone resulted in higher myeloperoxidase (MPO) activity, lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) than in the control. The enzyme activities did not change in rat given CAPE alone. CAPE treatment prevented the increase in MPO activity and malondialdehyde, but did not affect the activities SOD and CAT enzymes. CONCLUSION: In light of these results, we conclude that CAPE prevents MPO-and lipid peroxidation-mediated myocardial injury via inhibition of neutrophil's MPO activity.

Protective effect of thymoquinone in experimental testicular torsion.

OBJECTIVES: To investigate the protective role of thymoquinone (TQ) on unilateral testicular ischemia-reperfusion (I/R) injury in mice. MATERIALS AND METHODS: Experiments were performed on male C57BL/6 mice (8 weeks old, 20-25 g). The animals were divided into 3 groups including 6 mice in each group: control (sham), torsion/detorsion (TD) and TD+TQ. Mice, except the sham-operated group, were subjected to left unilateral torsion (720° rotation in the clockwise direction). The experiments were finished after sham operation time for controls, 120 min torsion and 240 min detorsion for the other groups. In the TD+TQ group 10 mg TQ was injected intraperitoneally 30 min before detorsion. RESULTS: In the TD group total oxidative stress (TOS), oxidative stress index (OSI) and malondialdehyde (MDA) levels were higher than in the controls. TQ treatment decreased MDA, TOS and OSI values, but did not affect the total antioxidant capacity and myeloperoxidase activity in the TD+TQ group. Upon histological examination, mice in the TD group displayed moderate-to-severe disruption of the seminiferous epithelium. Treatment with TQ resulted in significantly reduced histological damage associated with I/R injury. CONCLUSION: Our results suggested that TQ treatment may have a protective effect on testicular I/R injury.

Effects of ammonia and allopurinol on rat hippocampal NMDA receptors.

Ammonia is considered to be the main agent responsible for hepatic encephalopathy which progressively leads to altered mental status. N-methyl-D-aspartate (NMDA) is an ionotropic glutamate receptor, which is involved in synaptogenesis, memory and neurotoxicity. The aim of this study was to investigate the effects of ammonia intoxication and allopurinol, a xanthine oxidase (XO) inhibitor, on NMDA receptor subunits, NR2A and NR2B, in the hippocampus of rats. Thirty-six male rats were divided into three groups (n = 12/group) as follows: (1)control group (phosphate buffered saline (PBS) solution); (2)ammonia group (ammonium acetate, 2.5 mmol/kg), (3)ammonia + allopurinol group (ammonium acetate, 2.5 mmol/kg, allopurinol, 50 mg/kg). Each rat received intraperitoneal injection for 28 days. Western Blotting technique was used for detecting NR2A and NR2B expressions. Both NR2A and NR2B subunit expressions decreased 27 and 11%, respectively, in ammonia group with respect to the control group. Ammonium acetate decreased significantly in NR2A subunit expressions in the hippocampus (p < 0.01). Administration of ammonia + allopurinol caused statistically significant increases in NR2A subunit expressions compared to the ammonia group (p < 0.001). The down-regulation of NMDA receptors caused by ammonium acetate suggest that these receptors may play role in the process of hepatic encephalopathy and using allopurinol may have some protective effects in ammonia toxicity.

Increased amount of visceral fat in patients with psoriasis contributes to metabolic syndrome.

BACKGROUND: Psoriasis is associated with obesity and metabolic syndrome. Metabolic syndrome is associated with visceral fat accumulation. There is no study on the accumulation of visceral fat in patients with psoriasis. OBJECTIVE: The aim of this study was to compare the visceral fat accumulation in patients with psoriasis and controls. SUBJECTS AND METHODS: 46 patients with psoriasis and 46 sex- and age-matched control patients were included in this study. The abdominal fat area [visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA)] at the level of the umbilicus was evaluated by computed tomography. RESULTS: The mean VFA value and VFA/SFA ratio of the psoriasis patients were significantly higher compared with the control patients (123.4 +/- 80.3 vs. 81.2 +/- 59.8 cm(2) and 0.734 +/- 0.593 vs. 0.491 +/- 0.336; p = 0.005 and p = 0.017, respectively). Fasting blood sugar levels were also found to be significantly higher in psoriasis patients, compared with the control patients (101.8 +/- 43.5 vs. 83.4 +/- 9.1 mg/dl; p = 0.005). Multiple linear regression analysis indicated that waist-to-hip ratio, age, body weight, the presence of psoriasis and metabolic syndrome were significantly associated with VFA. CONCLUSION: Psoriasis patients had a higher amount of VFA, compared with the control patients.

Protective effects of tadalafil on experimental spinal cord injury in rats.

Tadalafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Nitric oxide (NO) functions as a retrograde neurotransmitter in the spinal cord, and postsynaptic structures respond to NO by producing cGMP. The concentrations of cGMP in the spinal cord are controlled by the actions of PDE. The aim of the study was to evaluate and compare the effects of the use of both methylprednisolone and tadalafil on serum and tissue concentrations of NO, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and tissue glutathione peroxidase (GSH-Px) activity in rats with spinal cord injury (SCI). SCI was induced in Wistar albino rats by dropping a 10 g rod from a 5.0 cm height at T8-10. The 28 rats were randomly divided into four equal groups: tadalafil, methylprednisolone, non-treatment and sham groups. Rats were neurologically tested at 24 hours after trauma. At the end of the experiment, blood samples were collected and spinal cord tissue samples were harvested for biochemical evaluation. The tissue level of NO was increased in the tadalafil group compared with the non-treatment and methylprednisolone groups (p<0.05). The tissue levels of SOD and GSH-Px did not differ between the groups. Serum levels of NO were higher in the tadalafil group than in the non-treatment group (p<0.05). The increase in serum SOD levels was greater in the tadalafil group than the methylprednisolone group. Serum MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group (p>0.05). Tissue MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group and sham groups (p>0.05). Although there was no difference in neurological outcome scores between the tadalafil, methylprednisolone and non-treatment groups (p>0.05), the animals in the tadalafil and methylprednisolone groups tended to have better scores than the non-treatment group. Thus, tadalafil appears to be beneficial in reducing the effects of injury to the spinal cord by increasing tissue levels of NO and serum activity of SOD.

Protective effect of caffeic acid phenethyl ester on cyclosporine A-induced nephrotoxicity in rats.

INTRODUCTION: Cyclosporine A, an immunosuppressive agent, is widely used after organ transplantation such as the liver and kidney. However, its widespread use is restricted because it has serious toxic effects on the kidney. Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti-inflammatory, antitumor, and antioxidant activities, and it attenuates inflammation and lipid peroxidation induced by ischemia-reperfusion injury. The purpose of the present study was to investigate the effects of CAPE on cyclosporine A (CsA)-induced nephrotoxicity. MATERIAL AND METHODS: Rats were divided into four groups and treated with saline, CAPE, CsA, and CsA + CAPE. Control rats were given saline; the CAPE group was given CAPE (10 micromol/kg/day) for 11 days intraperitoneally; the CsA group was given CsA (15 mg/kg/day) for 10 days subcutaneously; and the CsA+CAPE group was given CAPE for 11 days, and rats were s.c. injected with CsA in 0.5 ml of saline once a day for 10 days at the same time. RESULTS: The administration of CsA alone resulted in higher myeloperoxidase (MPO) activity, lipid peroxidation, superoxide dismutase (SOD), and catalase (CAT) than in the control. The enzyme activities except CAT in rats treated with CAPE alone were not changed. CAPE treatment prevented the increase in malondialdehyde (MDA) and increased CAT activity more, but did not affect the activities of MPO and SOD enzymes. DISCUSSION: CsA causes renal injury and CAPE prevents CAT- and lipid peroxidation-mediated nephrotoxicity via inhibition of oxidative process.

Resveratrol, a natural antioxidant, attenuates intestinal ischemia/reperfusion injury in rats.

The intestine is highly susceptible to ischemia/reperfusion (I/R) injury. Splanchnic ischemia is the initial event that releases injurious factors, leading to systemic disorders with high morbidity and mortality. Oxidative stress mediators are believed to contribute to the intestinal I/R injury. Resveratrol, a polyphenol found in grapes, is shown to be a strong antioxidant in various tissues, with a property of an estrogen-receptor agonist. Therefore, we investigated the effects of resveratrol on oxidative injury in the intestine. Female Wistar rats were randomly allocated into four groups (n = 8, each). The sham group was only subjected to surgical procedures, while other animals were subjected to intestinal ischemia (60 min) and subsequent reperfusion (60 min). One group received resveratrol (15 mg/kg, 0.3 ml/day intraperitoneally) for both 5 days before surgery and 15 min before ischemia, while the other was treated intraperitoneally with 0.5% ethyl alcohol as vehicle (0.3 ml/day). In the I/R rat intestines, we detected severe tissue injuries (p < 0.001), the significant increases in the tissue levels of malondialdehyde (MDA), nitric oxide (NO), and myeloperoxidase (MPO) (p < 0.001), and the decrease in superoxide dismutase (SOD) activity (p < 0.001), compared to the sham control. Resveratrol significantly ameliorated the intestinal injury, decreased MDA, NO and MPO levels to the sham control levels, and decreased bacterial translocation in mesentery lymph nodes, liver and spleen (p < 0.001). Resveratrol also restored the SOD activity. These results suggest that resveratrol could protect intestinal tissue against I/R injury with its potent antioxidant properties.

Gradual detorsion of torsioned rat testis attenuates ischemia reperfusion injury.

AIM: This study was designed to investigate effect of gradual detorsion on testicular ischemia reperfusion injury. MATERIALS AND METHODS: A total of 21 male rats were divided into 3 groups, each containing 7 rats. Torsion was created by rotating the left testis 720 degrees in a clockwise direction. Group 1 underwent sham operation. Group 2 (sudden detorsion) served as a torsion/detorsion group, receiving 2 hours torsion and 2 hours detorsion. In group 3, 360 degrees detorsion was done for 20 minutes after 720 degrees torsion for 2 hours. Then, testis was done full detorsion for 100 minutes. At the end of the experiments (fourth hour), left orchiectomy was performed to measure the tissue levels of malondialdehyde (MDA), superoxide dismutase, and glutathione peroxidase and to perform histologic examination in testes. RESULTS: The MDA levels of testis tissues were significantly increased in the sudden detorsion group as compared with the sham group. We found decrease of the MDA level in gradual detorsion group, but it was not a statistically significant amount. Significant decrease was found in the superoxide dismutase and glutathione peroxidase activities in the sudden detorsion group as compared with the sham and gradual detorsion groups. Histologic examinations were in accordance with the testicular tissue MDA levels. CONCLUSION: In the light of our biochemical and histopathologic findings, we can say that gradual detorsion has a trend to decrease the degree of testicular reperfusion injury in the rat torsion/detorsion model.

Effects of erdosteine on acetaminophen-induced hepatotoxicity in rats.

We investigated the effects of erdosteine on acetaminophen (APAP)-induced hepatotoxicity in rats. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), AST (aspartate aminotransferase), and ALT (alanine transaminase) activities, and malonyldialdehyde (MDA) and nitric oxide levels as oxidant/antioxidant biochemical parameters were investigated with light microscopic evaluation in adult female Wistar Albino rats. APAP administration produced a decrease in hepatic SOD, CAT, and GSH-Px activities, and coadministration of erdosteine (150 and 300 mg/kg) resulted in increases in the activities. MDA and NO levels increased in the APAP group, and erdosteine treatments prevented these increases. Significant elevations in serum AST and ALT levels were observed in the APAP group, and when erdosteine and APAP were coadministered, their serum levels were close to those in the control group. Light microscopic evaluation of livers showed that there were remarkable centrilobular (zone III) hepatic necrosis and mild to moderate sinusoidal congestion in the APAP group, whereas in the erdosteine group, cellular necrosis was minimal and the hepatocytes maintained a better morphology when compared to the APAP group. Erdosteine prevented APAP-induced liver injury and toxic side effects probably through the antioxidant and radical scavenging effects of erdosteine.

Protective effects of N-acetylcysteine on cyclosporine-A-induced nephrotoxicity.

OBJECTIVES: Cyclosporine A (CsA) is used for the treatment of autoimmune and inflammatory disorders. However, CsA-induced nephrotoxicity remains an important clinical problem, and oxidative stress has been implicated as a possible responsible mechanism. We assessed the protective ability of N-acetylcysteine (NAC), an antioxidant, against CsA-induced nephrotoxicity. MATERIALS AND METHODS: Wistar albino rats were randomly assigned into four groups. Group 1 rats were treated with sodium chloride as control, group 2 with CsA, group 3 with CsA and NAC, and group 4 with NAC alone. Animals were sacrificed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Kidney sections were analyzed for MDA and NO levels and SOD and GSH-Px activities, as well as histopathological changes. RESULTS: Overall, the treatment of rats with CsA alone produced significant increases in NO and MDA levels and significant decreases in SOD and GSH-Px activities in serum and renal samples. Morphological changes, including tubular epithelial atrophy, vacuolizations, and cellular desquamations, were clearly observed in the rats treated with CsA alone. Concurrent NAC administration with CsA improved renal function, as indicated by lower BUN and Cr values. Moreover, NAC significantly reduced MAD and NO levels and increased SOD and GSH-Px activities in serum and renal tissue, as well as provided a histologically proven protection against CsA-induced nephrotoxicity. CONCLUSION: These results indicate that NAC produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role for oxidative stress in pathogenesis.

From darkening urine to early diagnosis of alkaptonuria.

Alkaptonuria is a rare disorder of metabolism characterized by deficiency of homogentisic acid oxidase. Characteristic features include darkening of urine, ochronosis, and arthropathy. Darkening of urine is the only sign of the disorder in the pediatric age group, and it occurs at very early stage of the disorder, as reported by the parents. A 4-year-old boy presented to our clinic with the complaint of dark urine and bluish black staining of clothes. This darkening pointed to a positive physical history of bluish discoloration of sclerae which occurred off and on. We initiated treatment with ascorbic acid and a protein diet with restriction of phenylalanine and tyrosine (1.6 g/kg/d). This case report is significant because of the early diagnosis made.