1.Short-term exposure to gossypol causes reversible reproductive toxicity and nephrotoxicity in mice.
Hui WANG ; Zhi Yan PIAO ; Hui MA ; Lin Yu CAO ; Jun LIU ; Jun Zhu WU
Journal of Southern Medical University 2023;43(2):251-256
		                        		
		                        			OBJECTIVE:
		                        			To study the toxic effects of short-term exposure to gossypol on the testis and kidney in mice and whether these effects are reversible.
		                        		
		                        			METHODS:
		                        			Twenty 7 to 8-week-old male mice were randomized into blank control group, solvent control group, gossypol treatment group and drug withdrawal group. In the former 3 groups, the mice were subjected to daily intragastric administration of 0.3 mL of purified water, 1% sodium carboxymethylcellulose solution, and 30 mg/mL gossypol solution for 14 days, respectively; In the drug withdrawal group, the mice were treated with gossypol solution in the same manner for 14 days followed by treatment with purified water for another 14 days. After the last administration, the mice were euthanized and tissue samples were collected. The testicular tissue was weighed and observed microscopically with HE and PAS staining; the kidney tissue was stained with HE and examined for mitochondrial ATPase activity.
		                        		
		                        			RESULTS:
		                        			Compared with those in the control group, the mice with gossypol exposure showed reduced testicular seminiferous epithelial cells with rounded seminiferous tubules, enlarged space between the seminiferous tubules, interstitium atrophy of the testis, and incomplete differentiation of the spermatogonia. The gossypol-treated mice also presented with complete, non-elongated spermatids, a large number of cells in the state of round spermatids, and negativity for acrosome PAS reaction; diffuse renal mesangial cell hyperplasia, increased mesangial matrix, and adhesion of the mesangium to the wall of the renal capsule were observed, with significantly shrinkage or even absence of the lumens of the renal capsules and reduced kidney mitochondrial ATPase activity. Compared with the gossypol-treated mice, the mice in the drug withdrawal group showed obvious recovery of morphologies of the testis and the kidney, acrosome PAS reaction and mitochondrial ATPase activity.
		                        		
		                        			CONCLUSIONS
		                        			Shortterm treatment with gossypol can cause reproductive toxicity and nephrotoxicity in mice, but these toxic effects can be reversed after drug withdrawal.
		                        		
		                        		
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Gossypol/toxicity*
		                        			;
		                        		
		                        			Testis
		                        			;
		                        		
		                        			Seminiferous Tubules
		                        			;
		                        		
		                        			Spermatids
		                        			;
		                        		
		                        			Spermatogenesis
		                        			;
		                        		
		                        			Adenosine Triphosphatases/pharmacology*
		                        			
		                        		
		                        	
2.Inhibitory effect of extract of Coptidis Rhizoma on invasion of Candida albicans hyphae in vitro.
Hui-Xia NIU ; Qiang-Jun DUAN ; Gao-Xiang SHI ; Da-Qiang WU ; Jing SHAO ; Tian-Ming WANG ; Chang-Zhong WANG
China Journal of Chinese Materia Medica 2019;44(1):125-130
		                        		
		                        			
		                        			The aim of this paper was to investigate the inhibitory effect of extract of Coptidis Rhizoma(ECR) on invasion of Candida albicans hyphae in vitro.XTT reduction method was used to evaluate the metabolic activity of C.albicans.The colony edge growth of C.albicans was observed by solid medium.The growth of C.albicans hyphae was determined on semi-solid medium.The morphology and viability changes of C.albicans hyphae were assessed by scanning electron microscope and fluorescence microscope.qRT-PCR method was used to detect the ALS3 and SSA1 expression of C.albicans invasin genes.The results showed that the metabolic viability by XTT method detected that the activity of C.albicans was gradually decreased under the intervention of 64,128 and 256 mg·L-1 of ECR respectively.128,256 mg·L-1 of ECR significantly inhibited colony folds and wrinkles on solid medium and the hyphal invasion in semi-solid medium.Scanning electron microscopy and fluorescence microscopy showed that 128,256 mg·L-1 of ECR could inhibit the formation of C.albicans hyphae.qRT-PCR results showed that the expression of invasin gene ALS3 and SSA1 was down-regulated,and especially 256 mg·L-1 of ECR could down-regulate the two genes expression by 4.8,1.68 times respectively.This study showed that ECR can affect the invasiveness of C.albicans by inhibiting the growth of hyphae and the expression of invasin.
		                        		
		                        		
		                        		
		                        			Adenosine Triphosphatases
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Candida albicans
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Fungal Proteins
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Gene Expression Regulation, Fungal
		                        			;
		                        		
		                        			HSP70 Heat-Shock Proteins
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Hyphae
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			ultrastructure
		                        			;
		                        		
		                        			Microscopy, Electron, Scanning
		                        			
		                        		
		                        	
3.Effects of soybean isoflavones on the energy metabolism of swimming mice.
Bing-Nan DENG ; Jing-Ran SUN ; Hong JIN ; Hong-Jing NIE ; Rui-Feng DUAN ; Lie LIU ; Zhi-Xian GAO ; Zhao-Li CHEN
Chinese Journal of Applied Physiology 2018;34(1):39-42
		                        		
		                        			OBJECTIVE:
		                        			To establish an animal model for loaded swimming, so as to investigate the energy metabolism effects of soybean isoflavones (SI) on swimming mice.
		                        		
		                        			METHODS:
		                        			Thirty male Kunming mice were randomly divided into three groups:normal control, swimming group, and swimming+SI group. The normal control group mice were fed a basic AIN-93M diet, the SI groups were supplied with soybean isoflavones(4 g/kg).Two weeks later, the mice were forced to swim for an hour,and then all the mice were killed, the samples of blood, liver and muscles of hind were collected.The serum contents of lactic acid(Lac), the activities of lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), creatine kinase (CK) and ATPase were measured.
		                        		
		                        			RESULTS:
		                        			Compared with normal control,the serum content of Lac was significantly improved in the group of the swimming control and SI(<0.05),the activity of LDH in the serum was obviously improved in the group of the swimming control and SI, and the activity of CK and SDH were both significantly improved in the group of the swimming control and SI except the activity of SDH in the liver of the group SI; compared with the swimming control,the serum contents of Lac,the activities of LDH, ATPase, SDH, CK were obviously improved(<0.05).
		                        		
		                        			CONCLUSIONS
		                        			Soybean isoflavones can improve the energy metabolism,antioxidant capacity of the swimming mice.
		                        		
		                        		
		                        		
		                        			Adenosine Triphosphatases
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Creatine Kinase
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Energy Metabolism
		                        			;
		                        		
		                        			Isoflavones
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			L-Lactate Dehydrogenase
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Lactic Acid
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Random Allocation
		                        			;
		                        		
		                        			Soybeans
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Succinate Dehydrogenase
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Swimming
		                        			
		                        		
		                        	
4.Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder.
Rong-Yi ZHOU ; Jiao-Jiao WANG ; Yue YOU ; Ji-Chao SUN ; Yu-Chen SONG ; Hai-Xia YUAN ; Xin-Min HAN
Chinese Journal of Contemporary Pediatrics 2017;19(5):576-582
OBJECTIVETo study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD).
METHODSA total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA.
RESULTSCompared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P<0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium- and high-dose baicalin groups had a significant increase in the ATPase activity (P<0.05), a significant reduction in the LDH activity (P<0.05), and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P<0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05); the medium- and high-dose baicalin groups had a significant reduction in the LDH activity (P<0.05) and significant increases in the content of AC, cAMP, and PKA (P<0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P<0.05).
CONCLUSIONSBoth methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.
Adenosine Triphosphatases ; metabolism ; Adenylyl Cyclases ; physiology ; Animals ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; physiopathology ; Cyclic AMP ; physiology ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Flavonoids ; pharmacology ; therapeutic use ; L-Lactate Dehydrogenase ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Signal Transduction ; drug effects ; Synaptosomes ; chemistry ; ultrastructure
6.Effects of Radix aconiti lateralis preparata and Rhizoma zingiberis on energy metabolism and expression of the genes related to metabolism in rats.
Hua-Yun YU ; Shi-Jun WANG ; Jia-Lin TENG ; Xu-Ming JI ; Zhi-Chun WU ; Qing-Cui MA ; Xian-Jun FU
Chinese journal of integrative medicine 2012;18(1):23-29
OBJECTIVETo study the influence of Radix aconiti lateralis preparata and Rhizoma zingiberis, two species of Chinese medicinal herbs with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of their effects.
METHODSForty-eight specific pathogen free Wistar rats were randomly divided into a Radix aconiti lateralis preparata group, a Rhizoma zingiberis group, and a control group. They were intragastrically treated with concentrated decoction of Radix aconiti lateralis preparata, Rhizoma zingiberis and normal saline respectively for 20 days. Toe temperature (TT), energy intake (EI), digestible energy (DE), and metabolizable energy (ME) were measured. The content of adenosine triphosphate (ATP) and energy charge (EC) in hepatic tissue were measured with high performance liquid chromatography (HPLC). The activity of ATPase and succinate dehydrogenase (SDH) in the liver were detected with chemical colorimetry. The gene expression in the liver was detected with Illumina's rat Ref-12 gene array. The differential expression genes were selected, annotated and classified based on Gene Ontology (GO). Real-time quantitative reverse-transcriptase PCR (Q-RT-PCR) was used to test the accuracy of results.
RESULTSCompared with the control group, the TT on the 10(th) day after the beginning of administration and ATP in the Radix aconiti lateralis preparata and Rhizoma zingiberis groups increased significantly (P<0.05). EI/body mass (BM), DE/BM, ME/BM, the hepatic EC and the activity of Na(+)-K(+)-ATPase, Ca(2+)-Mg(2+)-ATPase and SDH of liver increased significantly only in the Radix aconiti lateralis preparata group (P<0.05). There were 592 differential expression genes in the Radix aconiti lateralis preparata group and 1 159 in the Rhizoma zingiberis group compared with the control group. Among the differential expression genes, genes related to metabolic processes were the most significant based on GO analysis. There were 337 strips of gene differential expression in common in both Radix aconiti lateralis preparata and Rhizoma zingiberis groups compared with the control group.
CONCLUSIONSHerbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.
Aconitum ; chemistry ; Adenosine Triphosphatases ; metabolism ; Adenosine Triphosphate ; metabolism ; Animals ; Body Temperature ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Energy Intake ; drug effects ; genetics ; Energy Metabolism ; drug effects ; genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Liver ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Rhizome ; chemistry ; Succinate Dehydrogenase ; metabolism
7.Studies on influence of Siwu decoction and its composite drugs on chemical-induced blood-deficiency model mice.
Min ZHU ; Jin'ao DUAN ; Yuping TANG ; Shulan SU ; Yongqing HUA ; Jianming GUO ; Dawei QIAN
China Journal of Chinese Materia Medica 2011;36(18):2543-2547
OBJECTIVETo investigate Siwu decoction and its composite drugs on the blood-deficiency model mice induced by acetylphenyhydrazine and cyclophosphamide.
METHODAcetylphenyhydrazine and cyclophosphamide were used to copy the blood-deficiency model mice. Automatic hematology analyzer was used to test the peripheral hemogram. Weighting method was used to test the liver index and spleen index; Kits for ATPase test was used to test the activities of Na+ - K+ - ATPase/Ca2+ - Mg2+ - ATPase in erythrocyte membrane. Flow cytometry was used to test the bone marrow cells' cell cycle.
RESULTAngelicar Sinensis Radix and Paeoniae Radix Alba had the most effective activity on the peripheral hemogram. Paeoniae Radix Alba, the drug pair including Angelicar Sinensis Radix and the drug- group including Paeoniae Radix Alba had the most effective activity on the liver index. All the drugs, drug-pairs, drug-groups and the formula had effect on the spleen index. To the activity of Na+ - K+ - ATPase in erythrocyte membrane, Rehmanniae Radix Praeparata, the drug-pairs and drug-groups including Angelicar Sinensis Radix exhibited the most effective activity. All the drugs, drug-pairs, drug-groups and the formula had the protective effect on the damaged bone marrow cells.
CONCLUSIONSiwu decoction and its composite drugs all had effect on the blood-deficiency model mice, but the action intensity was different. Angelicar Sinensis Radix and Paeoniae Radix Alba exhibited the most effective activity to the protection of the blood-deficiency model mice.
Adenosine Triphosphatases ; drug effects ; metabolism ; Angelica sinensis ; Animals ; Bone Marrow Cells ; drug effects ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cyclophosphamide ; Disease Models, Animal ; Drugs, Chinese Herbal ; metabolism ; pharmacology ; Female ; Glucosephosphate Dehydrogenase Deficiency ; chemically induced ; drug therapy ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; Mice ; Mice, Inbred ICR ; Paeonia ; Phenylhydrazines ; Protective Agents ; pharmacology ; Spleen ; drug effects ; metabolism
9.Effects of hydrogen sulfide on myocardial mitochondrial injury during acute myocardial ischemia in rats.
Fang LIU ; Jian-Xin ZHANG ; Lan-Fang LI ; Qin-Zeng ZHANG ; Yan-Yan DING ; Xin-Yan ZHANG
Chinese Journal of Applied Physiology 2011;27(2):158-162
OBJECTIVETo investigate the effect of hydrogen sulfide (H2S) on mitochondrial function in acute myocardial ischemia in rats.
METHODSAcute myocardial ischemia models were established by ligating the left anterior descending coronary artery (LADC) of rats. Fourty-eight male SD rats were randomly divided into 6 groups (n = 8): sham operation group, ischemia group, ischemia + sodium hydrosulfide (NaHS) low, middle and high dose groups and ischemia + DL-proparglycine(PPG) group. The ultrastructures of myocardial mitochondria were observed with electron microscope. The content of H2S in plasma and the activity of cystathionine-gamma-lyase (CSE) in myocardial tissue of rats were respectively detected. The swelling and activity of myocardial mitochondria were determined. The activities of ATPase, GSH-Px, SOD and the content of malondial-dehyde (MDA) in myocardial mitochondria of rats were also measured.
RESULTSCompared with those of the sham operation group, the content of H2S in plasma, the activity of CSE in myocardial tissue and the activity of myocardium mitochondria were significantly decreased. The activities of ATPase, SOD, GSH-Px in myocardial mitochondria were significantly decreased, The content of malondial dehyde(MDA) in myocardial mitochondria and the swelling of mitochondria were distinctly increased in the ischemia group (P < 0.01). Compared with those of the ischemia group, the content of H2S in plasma and the activity of CSE in myocardial tissue were increased, and the activities of mitochondria, ATPase, SOD, and GSH-Px in myocardial mitochondria were significantly increased in ischemia + NaHS low, middle and high-dose groups; the swelling of mitochondria and the content of MDA in myocardial mitochondria were significantly decreased in ischemia + NaHS middle and high-dose groups (P < 0.05 or P < 0.01). The administration of PPG could partially reduce the myocardial protection of hydrogen sulfide (P < 0.05 or P < 0.01).
CONCLUSIONIt could be concluded that the administration of hydrogen sulfide could enhance the activities of mitochondrial ATPase, SOD, GSH-Px, decrease the level of mitochondrial lipid peroxidation, and play a protective effect against acute myocardial ischemia.
Adenosine Triphosphatases ; metabolism ; Animals ; Glutathione Peroxidase ; metabolism ; Hydrogen Sulfide ; pharmacology ; Lipid Peroxidation ; drug effects ; Male ; Mitochondria, Heart ; drug effects ; metabolism ; physiology ; Myocardial Ischemia ; physiopathology ; prevention & control ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism
10.Effects of acetoacetate extract of Radix Aconite on hepatic contents of LA, LDH, PA, Gn and ATPase activities in deficient cold model rats.
Yi-yang LIU ; Shi-jun WANG ; Bing-bing HAN
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(11):1523-1526
OBJECTIVETo observe different effects of acetoacetate extract of Radix Aconite and Radix Aconite Decoction on the energy metabolism in deficient cold model rats.
METHODSWistar rats were randomly divided into the blank control group (n=10) and the deficient cold model group (n=30). The deficient cold rat model was established using decoction consisting of gypsum, Radix Gentianae, Cortex Phellodendri, and Rhizoma Anemarrhenae. The decoction was given to rats of the deficient cold model group by gastrogavage for 5 days. Then these rats were randomly divided into the acetoacetate extract of Radix Aconite group (n=10), the Radix Aconite Decoction group (n=10), and the model group (n=10). Rats in the model model group were administered with the decoction by gastrogavage. Rats in the other two groups were administered with the acetoacetate extract of Radix Aconite or Radix Aconite Decoction by gastrogavage for 5 days. The contents of lactic acid (LA), lactate dehydrogenase (LDH), pyruvate (PA), glycogen (Gn) and activities of Na(+) -K(+) -ATPase and Ca(2+) -Mg(2+) -ATPase in the hepatic tissue were detected.
RESULTSCompared with the blank control group, the PA content, activities of Na(+)-K(+) -ATPase and Ca(2+) -Mg(2+) -ATPase decreased in the model group. Compared with the model group, the PA content increased in the other two groups. Compared with the control group, the contents of LDH and PA, and activities of Na(+) -K(+) -ATPase increased in the the acetoacetate extract of Radix Aconite group with statistical difference (P < 0.05).
CONCLUSIONSThe febricity of acetoacetate extract of Radix Aconite was slightly higher than that of Radix Aconite Decoction, seemingly generating more energy. But the final conclusions and concrete mechanisms of action need further studies.
Acetoacetates ; Adenosine Triphosphatases ; metabolism ; Animals ; Disease Models, Animal ; Energy Metabolism ; drug effects ; Female ; Glycogen ; metabolism ; L-Lactate Dehydrogenase ; metabolism ; Lactic Acid ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Plant Extracts ; pharmacology ; Pyruvic Acid ; metabolism ; Rats ; Rats, Wistar
            
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