Morphine Enhances Deposition of Ferritin-Antiferritin Complexes in the Glomerular Mesangium

Abstract

Since increased mesangial accumulation of matrix has been considered to be an important event in the development of focal glomerulosclerosis, we investigated whether morphine, an active metabolite of heroin, can modulate mesangial accumulation of immune complexes. Control or morphine-dependent rats were administered intraperitoneal ferritin (8 mg/l00 g body weight) daily for 6 weeks. Body weight, blood pressure, serum creatinine, 24-hour urinary protein and creatinine excretion rates were measured at 3-week intervals. Rats were sacrificed at the end of 6 weeks and kidney tissue was studied by light, immunofluorescence and electron microscopy. Serum creatinine levels and urinary protein excretion rates were not different between control and morphine-dependent rats. All morphine-dependent rats developed hematuria, whereas only 1 control rat developed hematuria. Light microscopy revealed no proliferation of mesangial cells and only a minimal increase in the mesangial matrix. Electron-microscopic studies showed deposition of immune complexes in the mesangial region. Mesangial cells showed aggregation of ferritin in lysosomes. Immunofluorescence studies revealed the presence of IgG staining predominantly in the mesangial region. The majority (60%) of morphine-dependent rats showed a diffuse mesangial deposition of IgG when compared to control rats (83%) who showed only focal deposition. These results indicate that morphine enhances deposition of immune complexes in the mesangium. Morphine-induced enhanced deposition of macromolecules may not only alter the quantity of mesangial matrix but may also change its quality. This may play a pathogenic role in the development of glomerular lesions in patients who abuse opiates.

Morphine for the Treatment of Pain in Sickle Cell Disease

“…Morphine treatment led to albuminuria and podocyte injury as well as diminished expression of podocyte markers, synaptopodin, and nephrin, in wild type FVBN mice [ 10 ], and increased podocyte foot process effacement accompanied by albuminuria in sickle mice [ 60 ]. Morphine stimulates proliferation of glomerular mesangial cells [ 9 ] and superoxide production [ 58 ], enhances deposition of ferritin-antiferritin complexes in the glomerulus [ 61 ], amplifies nitrite production [ 62 ], and stimulates COX-2 in the kidneys of mice treated with morphine [ 54 ]. Morphine amplifies renal pathology, stimulates albuminuria, and impairs renal function, in sickle mice, which share the disease phenotype with humans [ 55 ].…”

Opioids and renal function

“…131 Morphine has been found to enhance capacity of mesangial cells to degrade increased amount of mesangial macromolecules. 149 Morphine enhances deposition of immune complexes in the mesangium by favoring the delivery or altering the exit of macromolecules such as human immunoglobulin G aggregates. 146 Morphine might play a role in the induction of mesangial injury in patients with opiate abuse, enhancing formation of superoxide by mesangial cells.…”

Apolipoprotein L1 (APOL1) Variants (Vs) a possible link between Heroin-associated Nephropathy (HAN) and HIV-associated Nephropathy (HIVAN)

“…In vivo studies, morphine inhibited matrix proteinases and promoted accumulation of matrix and IgG complexes in the mesangium (Sagar et al, 1994 ; Singhal et al, 1996a ). Morphine also enhanced accumulation of IgG complexes in the mesangium of rats with anti-thymoglobulin-induced kidney injury (Pan and Singhal, 1994 ; Singhal et al, 1996b ); additionally, it stimulated deposition of ferritin-antiferritin complexes in glomerular mesangium of rats (Singhal et al, 1995 ). Short-term administration of morphine invoked podocyte injury in the form of effacement of foot processes and down regulation of nephrin expression by podocytes (Lan et al, 2013 ).…”