Animals ; Animals, Newborn ; Hyperoxia ; physiopathology ; Lung ; drug effects ; pathology ; Oxygen ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; pharmacology ; therapeutic use

This study was aimed to investigate the effect of all-trans retinoic acid (ATRA) combined with SBA-Na on the biologic activities of human leukemia K562 and Kasumi-1 cell lines and their mechanism. The ATRA solution of 10(-6) mol/L (W1), 10(-4) mol/L (W2) and the SBA-Na solution of 100 µg/ ml (Z1) and 200 µg/ml (Z2) were prepared respectively. The K562 and Kasumi-1 cells were treated with W1, W2, Z1, Z2, W1 + Z1 and W2 + Z2 respectively, at same time, the blank control was set up. The cell morphology and growth in different treated groups were observed under light microscope. The CCK-8 method was used to detect the proliferation ability of cells, the cell growth curves were drawn, the inhibitory rate of cells was calculated. The flow cytometry with PI single staining and PI/Annexin V double stainings was used to detect the change of cell cycle and apoptosis of 2 cell lines treated with different drugs. The RQ-PCR was used to detect the change of Cyclin A mRNA expression in K562 cells. The results showed both ATRA and SBA-Na displayed inhibitory effect on cell proliferation, and the combination of these two drugs had stronger effect. As compared with the control group, the cell cycle distribution were changed obviously, and the apoptosis increased more significantly in treated groups, especially in group of ATRA combined with SBA-Na. The Cyclin A mRNA expression was up-regulated in Z1 group, while Cyclin A mRNA expression was down-regulated in other groups. It is concluded that both ATRA and SBA-Na can inhibit the proliferation of K562 and Kasumi-1 cell lines and promote their apoptosis. This effect may be stronger when both drugs combined. For K562 cells, the inhibitory effect may be accomplished through down-regulation of Cyclin A mRNA.
Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin A1 ; metabolism ; Deoxycholic Acid ; pharmacology ; therapeutic use ; Humans ; K562 Cells ; Tretinoin ; pharmacology ; therapeutic use

OBJECTIVETo explore the role of matrine (MAT) alleviating all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) and its mechanism.

METHODSATRA sensitive strain of APL (NB4) and resistant strain (NB4-R1, NB4-R2) were used in this study. The low toxic dosage of MAT was established by MTT test, and ATRA IC(50) of the cell strains (cultured with or without 0.1 mmol/L MAT) were obtained to confirm the reversal index (RI); the influence of MAT (10, 8, 6, 4, 2, 1, 0.1, 0.01, 0.001 mmol/L) combine with 1 µmol/L ATRA on the differentiation of the three cell strains were observed by nitro blue tetrazolium chloride (NBT) test and morphologic changes. The apoptosis rate of cells treated with different concentration of MAT combined with 1 µmol/L ATRA was tested by flow cytometry with Annexin V/PI staining.

RESULTS(1) The toxicity of MAT to NB4, NB4-R1, and NB4-R2 cells was increased with the concentration, IC(50) value was (0.661 ± 0.035) mmol/L, (0.673 ± 0.132) mmol/L and (0.329 ± 0.020) mmol/L, respectively; (2) After treated with 0.1 mmol/L MAT, the ATRA resistance factor of NB4-R1 decreased markedly (RI = 4.96 ± 1.15), but did not of NB4-R2(RI = 0.66 ± 0.17); (3) The differentiation capacity of NB4 and NB4-R1 was enhanced with increase of MAT, and peaked at 0.1 mmol/L (P < 0.05), but did not of NB4-R2; (4) After treated with MAT, the ATRA (1 µmol/L) induced apoptosis rate in NB4 and NB4-R1 increased significantly (P < 0.05 and P < 0.01, respectively).

CONCLUSIONMAT can reverse the ATRA resistance of NB4-R1, which may relate to the effect of MAT on differentiation and apoptosis. Treatment with MAT plus ATRA may exaggerate the cells resistance potency.

Alkaloids ; pharmacology ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Differentiation ; drug effects ; Drug Resistance, Neoplasm ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Quinolizines ; pharmacology ; therapeutic use ; Tretinoin ; pharmacology ; Tumor Cells, Cultured

PURPOSE: The aim of this study was to examine the effects of all-trans retinoic acid (ATRA) on diabetic nephropathy. MATERIALS AND METHODS: We measured amounts of urinary albumin excretion (UAE) after administrating ATRA to Otsuka Long-Evans Tokushima Fatty (OLETF) rats. In order to understand the mechanism of action for ATRA, we administrated ATRA to examine its inhibitory action on the production of transforming growth factor-beta1 (TGF-beta1), protein kinase C (PKC), and reactive oxidative stress (ROS) in cultured rat mesangial cells (RMCs). RESULTS: After 16 weeks of treatment, UAE was lower in the ATRA-treated OLETF rats than in the non-treated OLETF rats (0.07+/-0.03 mg/mgCr vs. 0.17+/-0.15 mg/mgCr, p<0.01). After incubation of RMCs in media containing 30 or 5 mM of glucose, treatment with ATRA showed time- and dose-dependent decreases in TGF-beta1 levels and ROS. Moreover, ATRA treatment showed a dose-dependent decrease in PKC expression. CONCLUSION: ATRA treatment suppressed UAE and TGF-beta1 synthesis, which was mediated by significant reductions in PKC activity and ROS production. Our results suggest that ATRA has a potential therapeutic role for diabetic nephropathy.
Animals ; Diabetes Mellitus, Type 2/*complications ; Diabetic Nephropathies/*complications/*drug therapy/pathology ; Mesangial Cells/*metabolism ; Oxidative Stress/drug effects ; Rats ; Rats, Inbred OLETF ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta1/analysis/pharmacology ; Tretinoin/*pharmacology/therapeutic use

OBJECTIVETo investigate the effect of organic gallium and gallium chloride on bone metabolism and their therapeutic effect against tretinoin-induced osteoporosis in rats.

METHODSRat models of osteoporosis was established with intragastric administration of tretinoin at the daily dose of 85 mg/kg for 15 days and randomized into control, organic gallium and gallium chloride groups. After administration of the corresponding treatments (none for the control group) for 4 weeks, the changes of the indices for osteoporosis were evaluated through biochemical and pathological approaches.

RESULTSTretinoin induced obvious changes in bone structure and contents of bone calcium and other elements, causing also significantly increased tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (AKP), which suggested the development of osteoporosis. Administration of organic gallium and gallium chloride treatments increased the bone density, bone cortex thickness and the percentage of bone trabecula, and Ga, Ca, P contents in the femur and teeth, but lowered the activity of TRAP and AKP, suggesting decreased bone conversion rate. Compared with gallium chloride, organic gallium required smaller dose with better safety to produce better therapeutic effect.

CONCLUSIONOrganic gallium can be safe and effective for treatment of tretinoin-induced osteoporosis in rats.

Animals ; Cell Line, Tumor ; Female ; Femur ; drug effects ; metabolism ; pathology ; Gallium ; chemistry ; pharmacology ; therapeutic use ; Hemodynamics ; drug effects ; Organometallic Compounds ; chemistry ; pharmacology ; therapeutic use ; Osteoporosis ; chemically induced ; drug therapy ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Tooth ; drug effects ; metabolism ; Trace Elements ; metabolism ; Tretinoin ; pharmacology

This study compared the decoction's HPLC figures of the different processed rhizomes of Cibotium barometz including the raw, the sand-baked, the wined, the steamed and the salted, on the basis of which, with the sand-baked Drynaria fortunei decoction as the positive control group, comparingall groups' decoction, concentration of which was 104.2 g x L(-1), for 4 weeks, by their effects (s-TRAP and total scores of OPG, Ca, P, IL-6, TNF-alpha and IL-1) on retinoic acid induced male rats osteoporosis. The experiment results showed the sand-baked and the wined were better than the steamed, the salted and the raw;in the processing methods' selection, the sand-baked was a better heating method than the steamed and the rice wine was the better excipient than the salt. It provided a reference to explain the processing principle of rhizomes of C. barometz and work mechanism of anti-osteoporosis.
Animals ; Biomarkers ; blood ; Chromatography, High Pressure Liquid ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Male ; Osteoporosis ; blood ; chemically induced ; drug therapy ; Pteridophyta ; chemistry ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Tretinoin ; adverse effects

OBJECTIVE: To examine the effects of ursolic acid (UA) on mitigating retinoic acid (RA)-induced osteoporosis in rats. METHODS: Fifty female Sprague-Dawley rats were randomly divided into the control group (n=10) and the osteoporosis group (n=40). The 40 osteoporosis rats were induced by 75 mg/(kg•d) RA once daily for 2 weeks, and then were randomly assigned to vehicle control (model), low-, middle-, and high-dose UA [(UA-L, UA-M, UA-H; 30, 60, 120 mg/(kg•d), respectively] groups (10 rats each). UA were administered once daily to the rats from the 3rd weeks for up to 4 weeks by gavage. Bone turnover markers [serum alkaline phosphatase (ALP), osteocalcin (OCN), urine deoxypyridinoline (DPD)] and other parameters, including serum calcium (S-Ca), serum phosphorus (S-P), urine calcium (U-Ca), urine phosphorus (U-P), and bone mineral density (BMD) of the femur, 4th lumbar vertebra and tibia, bone biomechanical properties and trabecular microarchitecture, were measured. RESULTS: The osteoporosis in rats was successfully induced by RA. Compared with the model group, UA-M and UA-H significantly reversed the RA-induced changes in S-P, U-Ca, U-P, ALP, OCN and urine DPD ratio and markedly enhanced the BMD of right femur, 4th lumbar vertebra and tibia (Plt;0.05 or Plt;0.01). Further, biomechanical test and microcomputed tomography evaluation also showed that UA-H drastically improved biomechanical properties and trabecular microarchitecture (Plt;0.05 or Plt;0.01). CONCLUSION UA could promote bone formation, increase osteoblastic activity and reduce osteoclastic activity in rats, indicating that UA might be a potential therapeutic of RA-induced acute osteoporosis.
Animals ; Biomechanical Phenomena ; Bone Density ; drug effects ; Bone Remodeling ; drug effects ; Female ; Osteoporosis ; diagnostic imaging ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; toxicity ; Triterpenes ; pharmacology ; therapeutic use ; X-Ray Microtomography

OBJECTIVETo explore the effect of combination of Epimedii Folium and Ligustri Lucidi Fructus on osteoporosis rats induced by retinoic acid.

METHODSixty three-month-old male Wistar rats were randomly divided into the normal control group, the model group, the Epimedii Folium group, the Ligustri Lucidi Fructus group, the combination group of Epimedii Folium and Ligustri Lucidi Fructus and the raloxifene group. The osteoporosis model was established through oral administration with retinoic acid for two weeks. Meanwhile, all of treatment groups were administered with corresponding drugs for three weeks. The contents of serum calcium (Ca), phosphorus (P), alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (StrACP) were detected, and the pathomorphological changes of femurs were observed.

RESULTThe model control group showed much lower contents of serum Ca and P than the normal control group, but with significantly higher AKP and StrACP activity than the normal control group. The femoral head area showed reduced, narrow and sparse trabecular bones, with typical osteoporosis-like changes. Compared with the model control group, all of treated groups showed significant increase in Ca and P contents in serum, and down-regulate AKP and StrACP levels, while trabecular bones became more and wider, and densely interweaved as a reticular formation. Among them, the combination group showed the most significant effect.

CONCLUSIONEpimedii Folium and Ligustri Lucidi Fructus could effectively correct the abnormal bone metabolism and improve pathological conditions of bone tissues, so as to show the anti-osteoporosis effect. The combined application of the two drugs showed a better efficacy.

Acid Phosphatase ; blood ; Alkaline Phosphatase ; blood ; Animals ; Body Weight ; drug effects ; Calcium ; blood ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epimedium ; chemistry ; Femur ; drug effects ; pathology ; Isoenzymes ; blood ; Ligustrum ; chemistry ; Male ; Osteoporosis ; blood ; chemically induced ; drug therapy ; pathology ; Phosphorus ; blood ; Rats ; Rats, Wistar ; Tartrate-Resistant Acid Phosphatase ; Tretinoin ; adverse effects