Schistosomiasis is the second most devastating tropical parasitic disease worldwide and is responsible for many urological complications. However, glomerular injury is a rare complication mainly described with Schistosoma mansoni. We report a case of membranoproliferative glomerulonephritis (MPGN) associated with Schistosoma hematobium infection in a young Senegalese boy living in a rural area. Clinical presentation was with steroid-resistant with nephrotic syndrome. Renal biopsy showed type 1 MPGN with the presence of S. hematobium eggs surrounded by a gigantocellular granuloma. Despite therapy with antihelminthic and immunosuppressive drugs, evolution was characterized by progression to end-stage renal disease over 1 year. More efforts should be made on the prevention and early detection of schistosomiasis among at-risk populations.
Conclusions: This case demonstrated the necessity of multiple immunomodulatory therapies for severe AAV. Treatment of relapses remains challenging especially for frequent relapses which required intensification of immunosuppressive regimen.Trimethoprim-sulfamethoxazole as PJP prophylaxis was evidencebased recommendation, which could also reduce the risk of relapse in GPA. Macrolide antibiotics are used primarily for prevention of bronchiectasis exacerbations as per European Respiratory Society guidelines. Anti-inflammatory effect of macrolide was well known in the literature, however macrolide effect on the autoimmune conditions has not been previously described.Previous studies suggested that bronchiectasis is highly prevalent in AAV, which was shown to be responsive to immunosuppression. There are no guidelines for using antibiotics for prevention in GPA with lower airway involvement. Thus this appears to be the first time in literature, macrolide antibiotics have been shown to be effective in suppressing flare ups of GPA. We think this strategy may be worth looking at if bronchiectasis or lower airway involvement exists prior to the onset of GPA.
This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15–120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.
Doxorubicin (DOX, Adriamycin), is a cancer chemotherapy agent used in the treatment regimen for breast, Hodgkin and Non‐Hodgkin lymphomas, small cell lung cancer and acute lymphoid leukemia. Unfortunately, doxorubicin clinical usage is associated with permanent cardiomyopathy and renal impairment. The cellular mechanisms for doxorubicin mediated renal cytotoxicity have yet to be understood. Resveratrol (RES) is a phytoalexin found in many fruits including grapes, blueberries, cranberries as well as chocolate and peanuts. Antioxidant and anticancer properties have been associated with RES in cell culture and in human clinical studies in cancer patients as well as animal models. This study tested the hypothesis that RES protection for DOX renal cytotoxicity, in human noncancerous renal proximal tubular epithelial cells (HK‐2), is mediated by preserving mitochondrial function and attenuating oxidative stress. HK‐2 cells were plated and grown in cell culture equilibrated for 48 h. Cells were next pre‐incubated for 1 h with 0 (DMSO) or 5 or 7.5 uM RES followed by a 24 h co‐incubation with 0–5 uM DOX. All results were obtained from 3 independent experiments. Western analysis probed for protein carbonylation was used as an indicator of oxidative stress. Mitochondrial function was assessed using a Seahorse analyzer system. Prior to examining mitochondrial function, cell number and substrate concentrations were optimized based on the manufacturer's recommendations. Mitochondrial Stress Test was conducted following the treatments described above and each well was normalized by protein. Western blot was conducted on whole cell lysate for SIRT1 and PGC1alpha. Viability was assessed using MTT leakage and tyrpan blue exclusion cell counts. RES did not alter cell viability as indicated by comparable MTT values between DMSO and RES groups (p>0.05). DOX was cytotoxic to HK‐2 cells within 24 h. Pretreatment with RES provided protection from DOX to HK‐2 cells. Mitochondrial respiration assessed as oxygen consumption rate (OCR) was diminished by DOX. DOX impaired mitochondria function within 24 h and RES provided protection. In summary, RES attenuated DOX renal cytotoxicity by maintaining mitochondrial function. Further studies are needed to probe changes in specific mitochondrial proteins mediated by DOX.Support or Funding InformationSupported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence. M.D. and R.M. supported by WV NASA Undergraduate Research Fellowship.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Doxorubicin (DOX, Adriamycin), is a cancer chemotherapy employed in the treatment regimen for breast, Hodgkin and Non‐Hodgkin lymphomas, small cell lung cancer and acute lymphoid leukemia. The U.S. FDA issued a Black Box warning for Cardiomyopathy in patients treated with doxorubicin. Other adverse effects include renal impairment. The cellular mechanisms for doxorubicin mediated renal cytotoxicity are not known. Resveratrol (RES) is a phytoalexin found in many fruits including grapes, blueberries, cranberries, dark chocolate and nuts. Antioxidant and anticancer properties have been associated with RES in cell culture and in human clinical studies in cancer patients and in vivo rodent models. Our studies tested the hypothesis that RES protection for DOX renal cytotoxicity, was mediated by maintaining mitochondrial function. All studies were conducted in human noncancerous renal proximal tubular epithelial cells (HK‐2). HK‐2 cells were plated and equilibrated for 48 h. Cells were next pre‐incubated for 1 h with 0 (DMSO) or 5 or 7.5 uM RES followed by a 24 h co‐incubation with 0–5 uM DOX. All results were obtained from 3 independent experiments. Western analysis for protein carbonylation and 4‐hydroxynooneal (4‐HNE) were used as an indicator of oxidative stress. Mitochondrial function was assessed using a Seahorse analyzer system. Prior to examining mitochondrial function, cell number and substrate concentrations were optimized based on the manufacturer’s recommendations. Mitochondrial Stress Test was conducted following the treatments described above and each well was normalized by protein. Viability was assessed using MTT leakage and tyrpan blue exclusion cell counts. RES did not alter cell viability as indicated by comparable MTT values between DMSO and RES groups (p>0.05). DOX was cytotoxic to HK‐2 cells within 24 h. Pretreatment with RES provided protection from DOX to HK‐2 cells. Basal mitochondrial respiration assessed as oxygen consumption rate (OCR) was diminished by 4 uM DOX. Mitophagy mediated by DOX and the effect of RES compared protein expression of LC3BI, LC3BII and the ratio of LC3BII/I. In summary, RES attenuated DOX renal cytotoxicity by maintaining mitochondrial function. Further studies are needed to probe changes in specific mitochondrial proteins mediated by DOX. Support or Funding Information (Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence; M.D. and R.M. supported by WV NASA Undergraduate Research Fellowship: M.D. Supported by MUSOM Summer Research Fellowship).
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