Acceleration of the Meckel Syndrome by Near-Infrared Light Therapy

BACKGROUND/AIMS Phototherapy using a narrow-band, near-infrared (NIR) light (using a light-emitting diode, LED) is being used to treat certain medical conditions. This narrow-band red light has been shown to stimulate cytochrome c oxidase (CCO) in mitochondria that would stimulate ATP production and has the ability to stimulate wound healing. LED treatment also decreases chemical-induced oxidative stress in tested systems. As renal cystic diseases are known to have evidence of oxidative stress with reduced antioxidant protection, we hypothesized that NIR light therapy might ameliorate the renal pathology in renal cystic disease. METHODS Wistar-Wpk/Wpk rats with Meckel syndrome (MKS) were treated with light therapy on days 10-18 at which time disease severity was evaluated. Wpk rats were either treated daily for 80 s with narrow-band red light (640-690 nm wavelength) or sham treated. At termination, renal and cerebral pathology was evaluated, and renal expression and activity of enzymes were assessed to evaluate oxidative stress. Blood was collected for blood urea nitrogen (BUN) determination, the left kidney frozen for biochemical evaluation, and the right kidney and head fixed for morphological evaluation. RESULTS There were no significant effects of LED treatment on body weight (BW) or total kidney weight in non-cystic rats. Total kidney weight was increased and anephric BW was decreased in cystic versus non-cystic controls. LED reduced BW and total kidney weight in cystic rats compared to non-light-treated cystic (control) rats. BUN was already increased almost 6-fold in cystic rats compared to control rats. BUN was further increased almost 2-fold with NIR treatment in both non-cystic and cystic rats compared to cystic and control rats. The hydrocephalus associated with Wpk/Wpk (ventricular volume expressed as total volume and as percent of anephric BW) was also more severe in NIR-treated cystic rats compared to the normal control rats. Renal glutathione peroxidase and catalase (CAT) were reduced in the cystic kidney while superoxide dismutase and CCO were increased. NIR increased CAT and CCO, marginally decreased glutathione S-transferase and slightly decreased glutathione reductase in cystic rats compared to the normal control rats. The detrimental effects of NIR may be related to reduced renal blood flow associated with progression of cystic pathology. Compression by cysts may not allow sufficient oxygen or nutrient supply necessary to support the increased oxidative phosphorylation-associated cellular activity, and the increased demand induced by NIR-increased CCO may have created further oxidative stress. CONCLUSION LED phototherapy initiated after the onset of symptoms was detrimental to MKS-induced pathology. NIR stimulates CCO thereby increasing the kidney's need for oxygen. We hypothesize that cystic compression of the vasculature impairs oxygen availability and the enhanced CCO activity produces more radicals, which are not sufficiently detoxified by the increased CAT activity.