Calcium oxalate stone disease: role of lipid peroxidation and antioxidants

Abstract

Membrane injury facilitated the fixation of calcium oxalate crystals and subsequent growth into kidney stones. Oxalate-induced membrane injury was mediated by lipid peroxidation reaction through the generation of oxygen free radicals. In urolithic rat kidney or oxalate exposed cultured cells, both superoxide anion and hydroxyl radicals were generated in excess, causing cellular injury. In hyperoxaluric rat kidney, both superoxide and H2O2-generating enzymes such as glycolic acid oxidase (GAO) and xanthine oxidase (XO) were increased, and hydroxyl radical and transition metal ions, iron, and copper were accumulated. The lipid peroxidation products, thiobarbituric acid-reactive substances (TBARS), hydroperoxides, and diene conjugates were excessively released in tissues of urolithic rats and in plasma of rats as well as stone patients. The accumulation of these products was concomitant with the decrease in the antioxidant enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glucose-6 phosphate dehydrogenase (G6PD) as well as radical scavengers, vitamin E, ascorbic acid, reduced glutathione (GSH), and protein thiol. All the above parameters were decreased in urolithic condition, irrespective of the agents used for the induction of urolithiasis. Oxalate binding activity and calcium oxalate crystal deposition were markedly pronounced, along with decreased adenosine triphosphatase (ATPase) activity. Lipid peroxidation positively correlated with cellular oxalate, oxalate binding, gamma-glutamyl carboxylase, and calcium level and negatively correlated with GSH, vitamin E. ascorbic acid, and total protein thiol. Antioxidant therapy to urolithic rats with vitamin E, glutathione monoester, methionine, lipoic acid, or fish oil normalised the cellular antioxidant system, enzymes and scavengers, and interrupted membrane lipid and protein peroxidation reaction, ATPase inactivation, and its associated calcium accumulation. Antioxidant therapy prevented calcium oxalate precipitation in the rat kidney and reduced oxalate excretion in stone patients. Similarly, calcium oxalate crystal deposition in vitro to urothelium was prevented by free radical scavengers such as phytic acid and mannitol by protecting the membrane from free radical-mediated damage. All these observations were suggestive of the active involvement of free radical-mediated lipid peroxidation-induced membrane damage in the pathogenesis of calcium oxalate crystal deposition and retention.

Oxalate: From the Environment to Kidney Stones

“…Given the fact that the growth time for a crystal to reach an obstructing diameter of ~200 μm is at least 1.5 h (46), it is highly unlikely that a crystal would attach to a healthy tubule with unobstructed urine fl ow (47,48). A crystal is more likely to attach and obstruct the urine fl ow if the primary injury is located in the anatomically narrow part of the tubule (46,48). Experiments in vitro, such as the one with MDCK cells (Madin-Darby canine kidney; cells with properties of distal tubule epithelial cells) (49), provided support for this theory.…”

Low-vitamin E diet exacerbates calcium oxalate crystal formation via enhanced oxidative stress in rat hyperoxaluric kidney

“…The principal causative agent for the formation of calcium salt crystals is thought to be supersaturation that causes the precipitation of salts in urine. However, even though urine is supersaturated with calcium and oxalate ions in normal subjects, stones do not form because of the presence of inhibitors and other unknown mechanisms (22).Membrane injury is suggested to be the primary event in CaOx crystal binding, and oxalate-induced free radicals are significant causative factors in membrane injury (11,12,25). This injury leads to lipid and protein peroxidation and altered biochemical reactions, including depletion of the antioxidant defense system (25).…”

“…Membrane injury is suggested to be the primary event in CaOx crystal binding, and oxalate-induced free radicals are significant causative factors in membrane injury (11,12,25). This injury leads to lipid and protein peroxidation and altered biochemical reactions, including depletion of the antioxidant defense system (25).…”

“…This injury leads to lipid and protein peroxidation and altered biochemical reactions, including depletion of the antioxidant defense system (25). On the basis of these findings, we hypothesized that if renal tubular injury due to increased oxidative stress caused by hyperoxaluria can be prevented, CaOx crystal accumulation in the kidneys can also be prevented.…”

Citrus Bioflavonoids Ameliorate Hyperoxaluria Induced Renal Injury and Calcium Oxalate Crystal Deposition in Wistar Rats

“…6 Studies had shown that supplementation of antioxidants provide cellular protection to the kidney, by inhibiting the over expression of inflammatory cytokines and improved the antioxidant status of the whole system. 7,8 Citrus fruit and their peels consist of a wide range of flavonoid compounds including Eriocitrin, Hesperidin, Naringin, Naringenin, which are known for its abilities to offer beneficial biological properties. 9 The major evident roles of citrus fruits in being a potential treatment for kidney stones were its ability to increase the urine pH and citrate content.…”