Nephrotoxic Effects Research Articles

Investigation of ochratoxin A (OTA) in bakers' urine samples in Istanbul by immunoaffinity column clean-up and high-performance liquid chromatography

Aim: Ochratoxin A (OTA), is the most toxic mycotoxin in the ochratoxins produced by Penicillium and Aspergillus species. It is known that this mycotoxin has carcinogenic, nephrotoxic, teratogenic, and immunotoxic effects. The aim of our study is the inhalation exposure of bakery workers to ochratoxin A, which can be found in flour. Materials and Methods: In this study, OTA occurrence and level in urine samples collected from bakers in Istanbul were analyzed by NaHCO₃ dilution, IAC (Immunoaffinity Column) clean-up, and high-performance liquid chromatography with fluorescent detection. Creatinine and malondialdehyde levels were measured spectrophotometrically in collected urine samples. Also, 8-hydroxy 2-deoxyguanosine which is a biomarker of DNA damage was tested by ELISA (Enzyme-Linked Immunosorbent Assay). Results: As a result of our study, the limit of detection (LOD) and the limit of quantification (LOQ) of the method were measured as 0.06 ngmLˉ¹ and 0.2 ngmLˉ,¹ respectively. Of the total collected urine samples 185, 4.9% were contaminated with OTA. Also, the statistically significant difference between OTA levels has not been determined in urine samples of bakers working at the production department and the bakers working at the other departments of the bakery (p>0.05). In order to define the exposure profile of OTA in bakers a questionnaire was conducted among the volunteers as well. But after the evaluation of the answers related to gender, age, dietary habits, coffee consumption, smoking, and alcohol consumption, no correlation was found with the OTA exposure (p>0.05). Conclusion: In the present study although OTA presence was not statistically significant, OTA detection in the urine of bakers’ indicates the necessity of regular follow-up for these workers.

Contrast-induced nephropathy; an update on pathophysiology

Contrast-induced nephropathy (CIN) is a well-known complication of contrast media administration for diagnostic and therapeutic purposes. The incidence of CIN has increased with the widespread use of diagnostic imaging and contrast media. CIN is a pathological condition that typically occurs within 48 hours of exposure to contrast material and results in an increase in serum creatinine levels of more than 44 µmol/L (0.5 mg/dL) or 25% above baseline or an increase in serum creatinine of more than 1.5 times the baseline level within 7 days of exposure to contrast material or a reduction in urine output to less than 0.5 mL/h for at least 6 hours after exposure to contrast material. The mechanism of CIN is not fully understood, but it is thought to involve direct nephrotoxic effects of contrast particles, hemodynamic changes, hypoxia and oxidative stress, apoptosis, inflammation, and immune responses. Prevention of CIN involves identifying the risk factors and taking appropriate measures to mitigate them. Currently, there is no definitive treatment for CIN, and treatment is mainly symptomatic, with supportive care being the mainstay. Experimental treatments such as renal replacement therapy, extracorporeal blood purification, and stem cell therapy are being investigated, but their clinical efficacy is yet to be established.

Četrdeset godina ciklosporina u kliničkoj praksi

Cyclosporine (CsA) was discovered in the lab of Sandoz in Switzerland in 1972. while searching for an antifungal drug. However, it quickly became an irreplaceable immunosuppressive drug for renal and other solid organ transplantation. It has been found, in the initial experiments, that CsA inhibits both in vitro cell-mediated lysis and lymphocyte sensitization by allogeneic target cells. Clinical trials have demonstrated better one-year graft survival after cadaveric renal transplants when receiving CsA instead of azathioprine. Although improvement has been observed in the rates of one-year renal graft survival and acute rejection, but long-term graft survival rate did not improve. This can be attributed to the nephrotoxic effects of the CsA. This issue is a consequence of hemodynamic effects on renal blood flow and glomerular filtration, effect on renal tubular function and blood vessels. Along with nephrotoxicity, CsA also causes other adverse effects such as hypertension, gingival hyperplasia, hyperkalemia, hypomagnesemia, hyperlipidemia, neurotoxicity, and in some cases thrombotic microangiopathies. However, in recent years CsA nephrotoxicity has been looked at from a different angle, where it has been linked to high CsA doses that used to be administered. Following its use in solid organ transplantation, CsA has been found to have an important role in treating systemic connective tissue diseases, as well as its consequences, primary glomerulonephritis, inflammatory bowel disease, and psoriasis. CsA effectiveness in treating above mentioned diseases is still greater than its side effects, which makes it a base of treatment options for numerous diseases.

Inhibition of the Mechanistic Targets of Rapamycin Beyond Transplant Immunosuppression: A Mini-Review

It has been about thirty years since identifying the target of rapamycin and using mTOR inhibitors in organ transplantation. There was a promise that they would replace calcineurin inhibitors with fewer nephrotoxic effects and better graft survival. Unfortunately, with time, the enthusiasm for using them in transplantation decreased due to the unpleasant profile of adverse events and limited evidence of tangible clinical benefit. With more understanding of physiology and judicious clinical application, new venues for mTOR inhibitors emerged. The mTOR pathway regulates primary cellular functions, including cell growth, metabolism, proliferation, and survival, and is critical for autophagy induction. Thus, as a master regulator, mTOR inhibitors emerged as anticancer therapies. In addition, such action proved beneficial for native or post-transplant malignancies. Signaling through components of the mTOR pathway is an essential regulator of normal cardiac growth and pathological hypertrophy. mTOR inhibitors are effective in reducing left ventricular thickness and mass. It could be an add-on benefit in kidney transplant recipients with high cardiovascular risk or attenuate cardiac allograft vasculopathy in heart transplant recipients. The mTOR inhibitors may help manage viral infections like cytomegalovirus, human herpesvirus 8-related Kaposi sarcoma, and possibly the BK virus. Furthermore, the mTOR pathway is modulated in many RNA viruses. Based on these facts, the idea of using mTOR inhibitors to treat COVID-19 infection has been evaluated. Accordingly, a new therapeutic role for mTOR inhibitors for treating COVID-19 infection t has emerged through reducing viral replication, and autophagocytosis, improving T cells function and preventing cytokine storm. This paper will review these applications of mTOR inhibitors beyond the horizon of transplant immunosuppression.

Histopathological Alterations in Nile Tilapia Oreochromis Niloticus (L.) as Influenced by Dietary Antiparasitic Drug Emamectin Benzoate at the Recommended and Higher Doses for an Extended Period

The effects of the dietary antiparasitic drug emamectin benzoate (EB) on the biosafety and kidney, liver and intestine tissue histopathology of Oreochromis niloticus were assessed. Extended EB medication at the recommended dose (50 μg/kg biomass/day) for 21 days reduced survival, feed intake and biomass. A dose-dependent hepatotoxic, nephrotoxic and intestinal toxic effects of EB were noticed. Tubular degeneration, glomerulopathy, inflammation and necrotized renal interstitium in the kidney and glycogen-type vacuolation and cytoplasmic degeneration in the liver were observed. The intestine exhibited loss of absorptive vacuoles, mucinous degeneration, necrotized intestinal villi and absorptive region and inflammation. Lamina propria swelling was noticed in the higher-dosed groups. With the termination of medication, the pathological changes were reduced significantly, indicating the ability of fish to mount adaptive responses to recoup. The extended EB administration for 21 days is unlikely to produce adverse and irrevocable effects on fish at the recommended dose.

Rhabdomyolysis following electical injury without acute kidney injury

Objective: Rhabdomyolysis is an important etiology for developing acute kidney injury (AKI). Among the many varying reasons for rhabdomyolysis, electrical injury seems to be a lesser-known factor. The clinical presentation of rhabdomyolysis is usually in the form of severe and widespread pain, tenderness, weakness in the muscles and dark urine. It is characterized by the disruption of cell integrity in myocytes as a result of widespread damage to skeletal muscles and the passage of intracellular components into the circulation. Case Presentation: Here we presented a case report of a young man who had rhabdomyolysis induced by electrical injury which is relatively less common among the other etiological factors with preserved renal functions. He had electrical injury related wounds on extremities. Urgent intravenous fluid therapy was initiated as soon as his admission to the emergency department (ED), without delay. Conclusion: AKI is very common due to the nephrotoxic effect of myoglobinuria and the prerenal status. It is rare that AKI does not develop in patients with a severe increase in creatinine kinase. It is a very important point to start effective fluid therapy in a short time.

Single-cell analysis of multiple cancer types reveals differences in endothelial cells between tumors and normal tissues

Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.

Subacute exposure to dimethoate induces hepatotoxic and nephrotoxic effects on male rats: Ameliorative effects of ferulic acid

Dimethoate commonly used as environmental ares for control pests which is widely used throughout in the world and itcaused toxic effects on nontarget organisms especially mammalian. Ferulic acid is known to protective compound generally used in toxicology studies. Thus, inthis study, we investigatedthe protective role of ferulic acid against the possible toxic effects of low and high doses of dimethoate. Male rats were randomly divided into six groups: control; ferulic acid; low and high dose dimethoate; both ferulic acid and low dose dimethoate; both ferulic acid and high dose dimethoate. The dimethoate treatment to rats caused oxidative stress in liver and kidney tissue via increased malondialdehyde levels and changes in superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase activities. All dose dimethoate treatments also caused histopathological alterations and differences in activities in alanine aminotransferase, aspartate aminotransferase, total protein, albumin, lactate dehydrogenase, total cholesterol, urea, uric acid, and creatinine levels. The histopathological results verified the biochemical findings for both liver and kidney. Co-administration of ferulic acid with dimethoate improved antioxidative parameters and eased some biochemical parameters mentioned above. Ferulic acid was also seen to play a beneficial role in the histopathological effects of dimethoate for both liver and kidney.

The ameliorating role of sofosbuvir and daclatasvir on thioacetamide-induced kidney injury in adult albino rats.

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

Biological and Medical Aspects Related to South American Rattlesnake Crotalus durissus (Linnaeus, 1758): A View from Colombia.

In Colombia, South America, there is a subspecies of the South American rattlesnake Crotalus durissus, C. d. cumanensis, a snake of the Viperidae family, whose presence has been reduced due to the destruction of its habitat. It is an enigmatic snake from the group of pit vipers, venomous, with large articulated front fangs, special designs on its body, and a characteristic rattle on its tail. Unlike in Brazil, the occurrence of human envenomation by C. durisus in Colombia is very rare and contributes to less than 1% of envenomation caused by snakes. Its venom is a complex cocktail of proteins with different biological effects, which evolved with the purpose of paralyzing the prey, killing it, and starting its digestive process, as well as having defense functions. When its venom is injected into humans as the result of a bite, the victim presents with both local tissue damage and with systemic involvement, including a diverse degree of neurotoxic, myotoxic, nephrotoxic, and coagulopathic effects, among others. Its biological effects are being studied for use in human health, including the possible development of analgesic, muscle relaxant, anti-inflammatory, immunosuppressive, anti-infection, and antineoplastic drugs. Several groups of researchers in Brazil are very active in their contributions in this regard. In this work, a review is made of the most relevant biological and medical aspects related to the South American rattlesnake and of what may be of importance for a better understanding of the snake C. d. cumanensis, present in Colombia and Venezuela.

Raman imaging studies on the stability of Paracetamol tablets under different storage conditions

The applicability of Raman imaging for pharmaceutics production ranges from the characterization of pharmaceutical formulations, kinetic processes in drug delivery to the rapid detection and identification of counterfeit drugs/contaminants. Acetaminophen (Paracetamol, APAP) is an analgesic and antipyretic drug and one of the most consumed medicines worldwide. On the other hand, the compound 4-aminophenol (4-AP) is a hydrolytic product of APAP with nephrotoxicity and teratogenic effects. In this work, we have explored for the first time Raman imaging methods to characterize the main components of commercial APAP tablets (APAP-tablets) and to inquire about the potential of this optical technique to identify 4-AP in APAP tablets, which have been previously spiked with such contaminant. The laboratorial treated APAP-tablet samples were subjected to different temperature, humidity and sunlight exposure conditions, mimicking storage conditions, and then the Raman spectra and images were collected to monitor changes that might occur in those conditions. Although the lower limit of detection of 4-AP in APAP-tablets is above the minimum levels established by Pharmacopoeias (0.005 %), this research demonstrates that Raman imaging still allows the detection of small amounts of the contaminant, thus opening perspectives for exploring this technique for characterizing APAP products.

Parametric MRI Detects Aristolochic Acid Induced Acute Kidney Injury.

Exposure to aristolochic acid (AA) is of increased concern due to carcinogenic and nephrotoxic effects, and incidence of aristolochic acid nephropathy (AAN) is increasing. This study characterizes renal alterations during the acute phase of AAN using parametric magnetic resonance imaging (MRI). An AAN and a control group of male Wistar rats received administration of aristolochic acid I (AAI) and polyethylene glycol (PEG), respectively, for six days. Both groups underwent MRI before and 2, 4 and 6 days after AAI or PEG administration. T2 relaxation times and apparent diffusion coefficients (ADCs) were determined for four renal layers. Serum creatinine levels (sCr) and blood urea nitrogen (BUN) were measured. Tubular injury scores (TIS) were evaluated based on histologic findings. Increased T2 values were detected since day 2 in the AAN group, but decreased ADCs and increased sCr levels and BUN were not detected until day 4. Significant linear correlations were observed between T2 of the cortex and the outer stripe of outer medulla and TIS. Our results demonstrate that parametric MRI facilitates early detection of renal injury induced by AAI in a rat model. T2 mapping may be a valuable tool for assessing kidney injury during the acute phase of AAN.

The Nephrotoxicity of Drugs Used in Causal Oncological Therapies.

In recent years, a dynamic development of oncology has been observed, resulting from the increasingly frequent occurrence of neoplasms and therefore, increasing population of patients. The most effective form of therapy for cancer patients is complex multidisciplinary specialized disease management, including nephro-oncology care. Different forms of renal function impairment are frequently diagnosed in cancer patients. They are caused by different co-morbidities existing before starting the oncologic treatment as well as the direct undesirable effects of this therapy which may cause temporary or irreversible damage of the urinary system-especially kidneys. According to different therapeutic programs, in such cases the degree of renal damage is often crucial for the possibility of further anti-cancer treatment. Medical personnel responsible for delivering care to oncology patients should be properly educated on current methods of prevention and treatment of renal complications resulting from anti-cancer therapy. The development of oncologic medicines design, including especially immuno-oncological agents, obliges us to learn new patomechanisms determining potential adverse effects, including renal complications. This publication is focused on the most important undesirable nephrotoxic effects of the frequently used anti-cancer drugs.

Ameliorative Effects of Propolis and Royal Jelly against CCl4 -Induced Hepatotoxicity and Nephrotoxicity in Wistar Rats.

Carbon tetrachloride (CCl4 ) is known to have hepatotoxic and nephrotoxic effects. During the two-month CCl4 exposure of Wistar rats, propolis extract (PE) and royal jelly (RJ) were added in order to test the potential protective effect against hepato-renal injury. Ketonuria, proteinuria, high creatinine and urea levels are the result of CCl4 -induced nephrotoxicity. Severe disorders of hematological indicators indicate anemia; high values of leukocytes indicate inflammatory condition. Cytogenetic impairments in hepatocytes, aggregation of platelets, and hypoproteinemia indicate severe liver impairment. Results suggest a more significant protective role of RJ compared to PE. Both extracts regulated proteinuria, ketonuria, hypoproteinemia and reduced platelet aggregation in the hepatic circulation. The increase in the number of erythrocytes (RBC) suggest protective effects against anemia; the decrease in the number of leukocytes can be linked to anti-inflammatory effects. PE and RJ have a beneficial effect against hepato-renal injury, anemia and anti-inflammatory conditions caused by CCl4 .

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

Safety of prescribed herbal medicines for hepatic and renal function of polypharmacy patients with stroke: A single-center retrospective study

In Korea, herbal medicines (HMs) are primarily used to treat diseases. Patients with stroke are generally older and take several conventional medicines (CMs) to address other underlying diseases, which is known as polypharmacy. Therefore, there is a growing concern about hepatotoxicity and nephrotoxicity due to drug interactions between HMs and CMs. Therefore, this study retrospectively investigated liver and renal tests in patients with stroke treated with polypharmacy to clarify the safety of simultaneous HM and CM administration. The medical records of 111 patients with stroke treated at a single center and who met the inclusion criteria between March 1, 2017, and March 1, 2022, were reviewed. The HMs and HM prescription frequency, CMs, and liver and kidney test results were recorded. Additionally, the Roussel Uclaf Causality Assessment Method and Kidney Disease Improving Global Outcome scores were documented, which are standard criteria for assessing liver and kidney injury, respectively. The study included 53 men and 58 women (average age: 67.8 years). On average, the patients took 6 types of CMs. No patient showed liver injury during the co-administration of CMs and HMs. Only 1 patient had initial hepatic damage but recovered after taking HMs. Furthermore, 2 patients had liver test abnormalities 2 times the upper limit of normal, possibly from Seogyeong-tang and atorvastatin, with Roussel Uclaf Causality Assessment Method scale scores of 3 and 5, respectively. No patient had a renal injury. HM is safe for patients with stroke taking multiple CMs. However, consulting an HM expert is essential to avoid hepatotoxicity, nephrotoxicity, and other adverse effects. These results highlight the benefits of Korea's dual medical system.

Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011–2022 review

Cisplatin (CDDP) is a well-known platinum-based drug used in the treatment of various malignancies. However, the widespread side effects that this drug leaves on normal tissues make its use limited. Since cisplatin is mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting complication attributed to cisplatin, which often leads to dose withdrawal. Considering the high efficiency of cisplatin in chemotherapy, finding renoprotective drug delivery systems for this drug is a necessity. In this regard, we can take advantages of different nanoparticle-based approaches to deliver cisplatin into tumors either using passive targeting or using specific receptors. In an effort to find more effective cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011–2022 review study was conducted to investigate some of the nanotechnology-based methods that have successfully been able to mitigate CDDP-induced nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria dysfunction, oxidative stress, lipid peroxidation and endoplasmic reticulum stress, some CDDP-based nano-carriers have been able to reverse a wide range of these advert effects. Based on the obtained results, it was found that the use of different metallic and polymeric nanoparticles can help renal cells to strengthen their antioxidant systems and stay alive through reducing CDDP-induced ROS generation, inhibiting apoptosis-related pathways and maintaining the integrity of the mitochondrial membrane. For example, nanocurcumin could inhibit oxidative stress and acting as a ROS scavenger. CONPs could reduce lipid peroxidation and pro-inflammatory cytokines. CDDP-loaded silver nanoparticles (AgNPs) could inhibit mitochondria-mediated apoptosis. In addition, tea polyphenol-functionalized SeNPs (Se@TE) NPs could mitigate the increased level of dephosphorylated AKT, phosphorylated p38 MAPK and phosphorylated c-Jun N-terminal kinase (JNK) induced by cisplatin. Moreover, exosomes mitigated cisplatin-induced renal damage through inhibiting Bcl2 and increasing Bim, Bid, Bax, cleaved caspase-9, and cleaved caspase-3. Hence, nanoparticle-based techniques are promising drug delivery systems for cisplatin so that some of them, such as lipoplatins and nanocurcumins, have even reached phases 1–3 trials.

Nephroprotective effects of Candesartan Cilexetil against Cyclosporine A-induced nephrotoxicity in a rat model.

Cyclosporine A (CsA), a well-known immunosuppressive drug, has been prescribed after organ transplantation and in a variety of disorders with an immunological origin. Nephrotoxicity is one of the most frequently stated problems associated with CsA, and therefore the treatment with CsA remains a big challenge. This study sets out to assess the ameliorative influences of Candesartan Cilexetil (CC) on oxidative stress and the nephrotoxic effect of CsA in a rat model. Twenty-four Wister Albino rats, 7-8-week-old, weighing 150-250g, were randomly categorized into three groups (eight animals in each group). These groups were the (1) CsA-treated group, (2) vehicle-treated group, and (3) CC-treated group. Bodyweights were assessed at the start and end of experiments. Renal function test and levels of glutathione peroxidase 1 catalase -CAT (Gpx1), catalase (CAT), superoxide dismutase (SOD), interleukin -2 (IL-2), and malondialdehyde (MDA) were investigated in renal tissues. Histological changes in kidneys were also evaluated. Data showed that levels of urea and creatinine in serum and levels of IL-2 and MDA in renal tissues were elevated in the CsA-treated group, with severe histological changes compared with the control group. Furthermore, tissue levels of Gpx1, CAT, and SOD were significantly decreased in CsA-treated in comparison with the control group. Treatment with CC for the rats subjected to CSA resulted in a marked reduction in levels of serum urea and creatinine and tissue levels of IL-2 and MDA. Levels of Gpx1, CAT, and SOD in renal tissues were greater in the CC-treatment group compared with the CsA-treated group. CC treatment reduced the deterioration of renal morphology compared with CsA treatment. The findings of this study suggest that CC could prevent CSA-induced nephrotoxicity through its anti-inflammatory and antioxidant influences. Considerably more work needs to be done to determine the mechanistic insight behind the ameliorative effect of CC.

Effect of coenzyme Q10 and vitamin E on gentamicin-induced nephrotoxicity in rats

Background/Aim: Gentamicin is an aminoglycoside antibiotic that can cause nephrotoxicity by damaging the kidneys due to high relative blood flow. In this study, the protective and therapeutic effects of CoQ10 and vitamin E on GM-induced nephrotoxicity were investigated. Methods: Fifty Wistar Albino rats were used as live material in this study, which were randomly divided into 5 groups of 10 animals. These groups, and the treatment they received, were as follows: a) control group: Physiological saline (i.p) for 8 days, b) GM group: Gentamycin 80 mg/kg/day/i.p for 8 days, c) GM+CoQ10 group: Gentamycin 80 mg/kg/day/i.p+ CoQ10 10 mg/kg/day/ i.p for 8 days, d) GM+ Vit E group: Gentamycin 80 mg/kg/day/i.p+ Vit E 250 mg/kg /day/ip administrated for 8 days, and e) GM+CoQ10+Vit E group: Gentamycin 80 mg/kg/day/ip + CoQ10 10 mg/kg/day/ip + Vitamin E 250 mg/kg /day/ip for 8 days. Following the test period, urea, creatinine, K, Na, Cl, retinol, vitamin D, and vitamin E levels of the subjects were measured in plasma, while MDA, GSH, AOPP, nitrite, nitrates, CAT, SOD, and GPx activities were measured in kidney tissues. Results: A severe nephrotoxic effect of GM administration in rats were detected as part of this study. The administration of CoQ10 and vitamin E, alone or in combination, was not sufficient to repair the kidney damage at the histopathological level. However, the renal tissue enzyme levels, along with other related to oxidative stress and plasma biochemical parameter analyses, were found to have improved greatly with the administration of vitamin E. Conclusion: CoQ10 and vitamin E can be suggested as supplementary agents to gentamicin treatment to prevent cell degeneration in the kidney and ensure healing

Possible nephrotoxic effects of high dose statin therapy; current knowledge

Possible nephrotoxic effects of high dose statin therapy; current knowledge