Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction via Nrf2/PINK1 Pathway

Previously, Our study has showed that farrerol can activate Nrf2 and ameliorate cisplatin-induced acute kidney injury (AKI). Mitophagy reportedly can prevent diabetic nephropathy, cisplatin-induced AKI and other related nephropathy. In this study, we evaluated the correlation between mitophagy and the protective effect of the Nrf2 activator farrerol on cisplatin-induced CKD by using C57BL/6 wild-type and Nrf2 knockout mice. We confirmed that Nrf2 and PINK1/Parkin-mediated mitophagy was significantly increased on the 3rd day of cisplatin stimulation but was reduced on the 38th day of cisplatin stimulation. Similar to previous results, farrerol activated Nrf2 on the 38th day of cisplatin administration, subsequently stimulating the Nrf2-targeted antioxidant enzymes HO-1 and NQO1. In addition, farrerol triggered PINK1/Parkin-mediated mitophagy by recruiting the receptor proteins LC3 and p62/SQSTM1, thereby eliminating damaged mitochondria. Furthermore, genetic deletion of Nrf2 reduced PINK1/Parkin-mediated mitophagy activation and led to increased renal tubular necrosis and renal fibrosis. We also found that farrerol alleviated inflammation and renal fibrosis by inhibiting p-NF-κB/NLRP3 and TGF-β/Smad signaling. These data indicated that farrerol effectively inhibited cisplatin-induced inflammation and renal fibrosis by activating Nrf2 and PINK1/Parkin-mediated mitophagy, which provides a potential novel therapeutic target for CKD.

Spontaneously Occurring Chronic Copper Toxicosis in Pattanam Breed of Sheep

Background: Copper (Cu), an essential trace element, is toxic if consumed in excessive amounts. Ruminants, particularly sheep, are highly susceptible to chronic copper poisoning and cause acute death. Spontaneous copper poisoning in sheep was reported from many parts of the world however limited reports are available from India. Hence the present investigation was undertaken to report the occurrence of chronic copper poisoning in an intensively maintained Pattanam breed of sheep flock and its therapeutic management. Methods: An investigation was carried out to ascertain the possible cause of increased mortality in an intensively maintained 130 male lambs aged between 8 to 10 month old belongs to Pattanam breed during the month of September 2020 following death of 21 animals within a period of 15 days. Affected flock was inspected and samples were collected for biochemical analysis, toxicological, bacteriological and pathological examination.Result: Affected animals showed depression, anorexia, jaundice, hemoglobinurea and accelerated breathing. At necropsy, the dead animals showed generalized icterus, lung edema, yellow to orange coloured liver and gun metal kidney. Histopathological lesions include lung edema, centrilobular hepatic necrosis, bile stasis, renal tubular necrosis and formation of tubular cast. Toxicological analysis of liver revealed the copper level of 781 mg/kg dry matter basis. Source of copper was identified as a commercial mineral mixture supplement intended for cattle was supplemented along with concentrate feed. The flock was treated with chelating agent (D-penicllamine) and supportive therapies.

CLINICAL, HAEMATOLOGICAL AND PATHOLOGICAL CHANGES FOLLOWING BILATERAL URETERAL LIGATION IN BORNO WHITE GOATS A PRELIMINARY REPORT.

Bilateral ureteral ligation was performed through the left paralumbar fossa in 4 clinically healthy adult Borno White goats. Clinical effects of uraemia were observed 24 hours after surgery when anuria had set in and included in appetence, depression, coughing, stretching of the neck, laboured breathing with inspiratory wheezing sound, serous to mucous ocular and nasal discharges, and terminal paralysis and convulsion. Haematological changes observed included anaemia from day 2 after surgery and lymphocytosis on days 1 and 2, leukocytosis on day 3, neutrophilia on days 3 and 5 and eosinopenia on days 9 and 11 after Surgery. At post-mortem, the major lesions observed were bronchopneumonia, renal tubular necrosis and gastroenteritis.

GAMBARAN HISTOLOGI GINJAL MENCIT JANTAN (Mus musculus) YANG DIBERI EKSTRAK BUAH JUWET (Syzygium cumini) SEBAGAI PELURUH RADIKAL BEBAS PADA ASAP ROKOK

Tujuan penelitian ini adalah untuk untuk mengetahui pengaruh pemberian ekstrak buah juwABSTRAKLatar Belakang : Tujuan penelitian ini adalah untuk untuk mengetahui pengaruh pemberian ekstrak buah juwet (Syzygium cumini) terhadap histologi ginjal mencit jantan (Mus musculus) yang terpapar asap rokok.Metode : Rancangan percobaan yang digunakan adalah Rancangan Acak Lengkap (RAL). Penelitian ini menggunakan 3 kelompok mencit jantan yang terdiri dari control (P0) diberi air minum sebanyak 0,2 ml, perlakuan 1 (P1) diberi paparan asap rokok, dan perlakuan 2 (P2) diberi ekstrak buah juwet sebanyak 0,2 ml dan paparan asap rokok. Semua kelompok perlakuan dilakukan selama 36 hari. Data hasil penelitian diolah dan disajikan dalam bentuk tabel menggunakan program statistik komputer (SPSS 20.0 for Windows) dengan menggunakan uji One Way Anova.Hasil : Hasil penelitian menunjukkan bahwa pemberian ekstrak buah juwet berpengaruh signifikan (P<0,05) terhadap jumlah nekrosis glomerulus dan tubulus ginjal mencit jantan yang terpapar asap rokok.Kesimpulan : pemberian ekstrak buah juwet (Syzygium cumini) sebanyak 0,2 ml dapat menurunkan jumlah nekrosis glomerulus dan tubulus ginjal mencit jantan (Mus musculus) yang terpapar asap rokok. Kata kunci: asap rokok, ekstrak buah juwet, nekrosis glomerulus, nekrosis tubulus, ginjal ABSTRACTIntroduction : The purpose of this research is to prove the effects of the java plum fruit extract to the necrosis of glomerulus and tubule of the kidney of cigarette smoke exposed mice.Method : The experimental design used within study was a Completely Randomised Design (CRD) with three groups: control (P0) treated with water 0,2 ml, P1 treated with cigarette smoke exposed, and P2 treated with java plum fruit extract treatment 0,2 ml and cigarette smoke exposed. All Treatment and exposure cigarette smoke was given about 36 days. Data were analyzed with statistic program (SPSS 16.0 for Windows) with One Way Annova.Result : The result showed that the extract java plum fruit significantly increased (P<0,05) the number of necrosis of glomerulus and tubule of the kidney of cigarette smoke exposed mice.Conclusion : giving 0.2 ml of juwet fruit extract (Syzygium cumini) can reduce the amount of glomerular necrosis and renal tubular necrosis of male mice (Mus musculus) exposed to cigarette smoke. Keywords: Cigarrete smoke, java plum fruit extract, necrosis of glomerulus, necrosis of tubule, kidneyet (Syzygium cumini) terhadap histologi ginjal mencit jantan (Mus musculus) yang terpapar asap rokok. Rancangan percobaan yang digunakan adalah Rancangan Acak Lengkap (RAL). Penelitian ini menggunakan 3 kelompok mencit jantan yang terdiri dari control (P0) diberi air minum sebanyak 0,2 ml, perlakuan 1 (P1) diberi paparan asap rokok, dan perlakuan 2 (P2) diberi ekstrak buah juwet sebanyak 0,2 ml dan paparan asap rokok. Semua kelompok perlakuan dilakukan selama 36 hari. Data hasil penelitian diolah dan disajikan dalam bentuk tabel menggunakan program statistik komputer (SPSS 20.0 for Windows) dengan menggunakan uji One Way Anova. Hasil penelitian menunjukkan bahwa pemberian ekstrak buah juwet berpengaruh signifikan (P<0,05) terhadap jumlah nekrosis glomerulus dan tubulus ginjal mencit jantan yang terpapar asap rokok. Kata kunci: asap rokok, ekstrak buah juwet, nekrosis glomerulus, nekrosis tubulus, ginjal

Pathology and Epidemiology of Oxalate Nephrosis in Cheetahs

To investigate cases of acute oxalate nephrosis without evidence of ethylene glycol exposure, archived data and tissues from cheetahs ( Acinonyx jubatus) from North America ( n = 297), southern Africa ( n = 257), and France ( n = 40) were evaluated. Renal and gastrointestinal tract lesions were characterized in a subset of animals with ( n = 100) and without ( n = 165) oxalate crystals at death. Crystals were confirmed as calcium oxalate by Raman spectroscopy in 45 of 47 cheetahs tested. Crystals were present in cheetahs from 3.7 months to 15.9 years old. Cheetahs younger than 1.5 years were less likely to have oxalates than older cheetahs ( P = .034), but young cheetahs with oxalates had more oxalate crystals than older cheetahs ( P < .001). Cheetahs with oxalate crystals were more likely to have renal amyloidosis, interstitial nephritis, or colitis and less likely to have glomerular loop thickening or gastritis than those without oxalates. Crystal number was positively associated with renal tubular necrosis ( P ≤ .001), regeneration ( P = .015), and casts ( P ≤ .001) but inversely associated with glomerulosclerosis, renal amyloidosis, and interstitial nephritis. Crystal number was unrelated to the presence or absence of colitis and was lower in southern African than American and European animals ( P = .01). This study found no evidence that coexisting chronic renal disease (amyloidosis, interstitial nephritis, or glomerulosclerosis), veno-occlusive disease, gastritis, or enterocolitis contributed significantly to oxalate nephrosis. Oxalate-related renal disease should be considered as a potential cause of acute renal failure, especially in young captive cheetahs. The role of location, diet, stress, and genetic predisposition in the pathogenesis of oxalate nephrosis in cheetahs warrants further study.

Peptidyl arginine deiminase-4-deficient mice are protected against kidney and liver injury after renal ischemia and reperfusion

We previously demonstrated that renal peptidyl arginine deiminase-4 (PAD4) is induced after renal ischemia and reperfusion (I/R) injury and exacerbates acute kidney injury (AKI) by increasing the renal tubular inflammatory response. Here, we tested whether genetic ablation of PAD4 attenuates renal injury and inflammation after I/R in mice. After renal I/R, PAD4 wild-type mice develop severe AKI with large increases in plasma creatinine, neutrophil infiltration, as well as significant renal tubular necrosis, apoptosis, and proinflammatory cytokine generation. In contrast, PAD4-deficient mice are protected against ischemic AKI with reduced real tubular neutrophil infiltration, renal tubular necrosis, and apoptosis. In addition, hepatic injury and inflammation observed in PAD4 wild-type mice after renal I/R are significantly attenuated in PAD4-deficient mice. We also show that increased renal tubular PAD4 expression after renal I/R is associated with translocation of PAD4 from the nucleus to the cytosol. Consistent with PAD4 cytosolic translocation, we show increased renal tubular cytosolic peptidyl-citrullination after ischemic AKI. Mechanistically, recombinant PAD4 treatment increased nuclear translocation of NF-κB in cultured human as well as murine proximal tubule cells that is inhibited by a PAD4 inhibitor (2-chloroamidine). Taken together, our studies further support the hypothesis that renal tubular PAD4 plays a critical role in renal I/R injury by increasing the renal tubular inflammatory response and neutrophil infiltration after renal I/R perhaps by interacting with the proinflammatory transcription factor NF-κB in the cytosol and promoting its nuclear translocation.

DRUG INDUCED ACUTE TUBULAR NECROSIS – RARE CASE OF NEPHROTIC SYNDROME

We presented two cases of nephrotic syndrome (NS) drug-induced with tubular nephrotoxicity, with different evolution in the context of etiologic diseases. First is 5-month-old girl admitted with NS (clinically and biological proven) and acute renal failure after another hospitalization for pneumonia. The girl was treated with ceftriaxone and gentamicin 12 days. Congenital NS suspicion was eliminated by renal biopsy who revealed renal tubular necrosis highlighting recovery phase. The development was favorable in 7 days of peritoneal dialysis. The second case was 16 years old adolescents treated 3 years with carbimazol for Basedow disease. Was presented with nephrotic syndrome not influenced by corticosteroids. Histopathology revealed toxic tubular necrosis, interstitial fibrosis, absence of glomerular injury. Nephrotoxic treatment was stopped, and, after thyroidectomy, edema were reduced, but kidney function continued to depreciate, while nephrotoxic therapy given for 3 years. Conclusions. Renal tubular necrosis clinical and laboratory expressed by nephrotic syndrome, accompanied by renal insufficiency is a rare occurrence in children; gentamicin and carbimazol can be criminalized. The suffering or impairment may be improved by removing the causative drug. Treatment failure was associated with duration of drug aggression and evolution of comorbidities.