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This study was designed to investigate effects of raloxifene (RLX) and estradiol on bone formation and resorption in intact and ovariectomized (ovx) rat models. In the intact model, a total of 24 adult female rats were divided into three groups: Controls subcutaneously received saline alone. RLX (2 mg/kg) and estradiol (30 microg/kg) were injected to two groups of animals for a period of 6 weeks at two daily intervals. In the second model, rats (n = 24) were ovx and allowed to recover for a period of at least 3 weeks. Control group received vehicle alone. Remaining rats were divided into two groups and injected with RLX (2 mg/kg) and estradiol (30 microg/kg) for 6 weeks. Urine samples were collected from all animals 24 h after the last drug administration. Urinary deoxypyridinoline (DPD) was measured by ELISA. Serum parathyroid hormone (PTH), calcitonin, and osteocalcin levels were measured by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), Ca, and inorganic phosphate were determined by enzymatic-colorimetric method. Lumbar vertebrae (L2) of all animals were dissected out and processed for histopathological evaluation. Removal of ovaries significantly elevated urinary DPD levels (p < 0.01) compared with intact controls. Treatment of both intact and ovx rats with estradiol resulted in significant decreases (p < 0.01) in DPD values. RLX administration had no significant effect in the intact rats, but it remarkably reduced bone turnover in the ovx animals (p < 0.001). Both estradiol and RLX produced conflicting effects on serum ALP, osteocalcin, and PTH levels in both animal models. These findings suggest that RLX exerts its protective effects by reducing bone resorption, similar to that of estradiol, in ovx rats.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats., (Copyright 2005 John Wiley & Sons, Ltd.)

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Two PCB mixtures, Aroclors 1221 and 1254 have been suggested to have estrogenic and anti-estrogenic properties, respectively. We have examined whether these PCB mixtures modulate bone turnover and vertebral histology in intact and ovariectomized (ovx) rat models. Thirty-two adult female rats were divided into four groups subcutaneously receiving 4% DMSO (control), A1221 (10 mg/kg), A1254 (10 mg/kg) oestradiol (E2, 30 microg/kg). These compounds were injected to the animals for a period of 6 weeks at two daily intervals. In the second model, rats (n=32) were ovx and allowed to recover for a period of 3 weeks. Control group received vehicle (4% DMSO) alone. Remaining rats were divided into three groups and injected (s.c.) with A1221, A1254 and E2 for 5 weeks. Urine samples were collected prior to end of the experiments. Then, all animals were decapitated. Serum parathyroid hormone (PTH), calcitonin and osteocalcin levels were determined by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), calcium and inorganic phosphate were determined by enzymatic-colorimetric method. Urinary deoxypyridinoline (DPD) was measured by ELISA. Lumbar vertebrae (L2) of all animals were dissected out and processed for light microscopy. Levels of urinary DPD were significantly lowered in E2 -treated intact rats (p<0.001). Ovx significantly increased urinary DPD excretion (p<0.01) compared to intact control values. Administration of A1221 and A1254 had no significant effects in intact rats, however, they significantly reduced (p<0.05) and increased (p<0.001) urinary DPD levels in ovx rats, respectively. Neither of the PCB mixtures significantly changed serum osteocalcin and ALP levels in intact or ovx rats (except A1221 increased ALP in intact model, p<0.01). Both PCB mixtures had differential effects on serum PTH, calcitonin, calcium and inorganic phosphate concentrations. Treatment with A1221 reversed the adverse effects of ovariectomy on L2 histology. However, A1254 produced necrotic areas in vertebral bone, and this effect was expanded in ovx animals. Our findings suggest that both Aroclor compounds interfere with bone turnover mechanisms, particularly in ovx rats.