Magnetic Resonance Imaging for Rapid Screening for the Nephrotoxic and Hepatotoxic Effects of Microcystins

Abstract

In vivo visualization of kidney and liver damage by Magnetic Resonance Imaging (MRI) may offer an advantage when there is a need for a simple, non-invasive and rapid method for screening of the effects of potential nephrotoxic and hepatotoxic substances in chronic experiments. Here, we used MRI for monitoring chronic intoxication with microcystins (MCs) in rat. Male adult Wistar rats were treated every other day for eight months, either with MC-LR (10 μg/kg i.p.) or MC-YR (10 μg/kg i.p.). Control groups were treated with vehicle solutions. T1-weighted MR-images were acquired before and at the end of the eight months experimental period. Kidney injury induced by the MCs presented with the increased intensity of T1-weighted MR-signal of the kidneys and liver as compared to these organs from the control animals treated for eight months, either with the vehicle solution or with saline. The intensification of the T1-weighted MR-signal correlated with the increased volume density of heavily injured tubuli (R2 = 0.77), with heavily damaged glomeruli (R2 = 0.84) and with volume density of connective tissue (R2 = 0.72). The changes in the MR signal intensity probably reflect the presence of an abundant proteinaceous material within the dilated nephrons and proliferation of the connective tissue. T1-weighted MRI-is a valuable method for the in vivo screening of kidney and liver damage in rat models of intoxication with hepatotoxic and nephrotoxic agents, such as microcystins.

Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice

“…Li et al [23] revealed that kidney was injured by destroying renal corpuscle and renal tubules after intraperitoneal injection of extracted microcystins in omnivorous crucian carp (Carassius auratus). In our study, pathological lesions were observed and characterized by enlarged renal corpuscles with compressed Bowman's space, widened of kidney tubules, and lymphocyte infiltration in the interstitial tissue and the renal pelvis which were consistent with the findings of previous studies [40]. Combined with the findings of previous studies, it can be concluded that exposure to MC-LR could negatively affect kidney through pathological lesions.…”

Nonalcoholic fatty liver disease alters microcystin-LR toxicokinetics and acute toxicity

“…In a cohort of fisherman with an estimated MC exposure between 2.2-3.9 μg/day, serum MC concentrations correlated with the plasma levels of ALT and AST (24). To date, a link between MC exposure and kidney disease has not been demonstrated, although substantial preclinical data indicate that renal toxicity is also associated with MC exposure (25)(26)(27)(28)(29)(30)(31)(32)(33).…”

Toxic mechanisms of microcystins in mammals

“…Researchers from the University of Ljubljana in Slovenia have conducted several well-controlled in vivo studies on the effects of chronic exposure to MCs on rat organs. 30,80,81 Recent Chinese studies from Nanjing University and environmental groups have also explored the effects of exposure to MCs on mammalian cardiac and reproductive organs. Collectively, these studies lend to elucidating the mechanisms of toxicity by MCs on various mammalian organs and tissues.…”