2.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
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Male
;
Animals
;
Gossypol/toxicity*
;
Testis
;
Seminiferous Tubules
;
Spermatids
;
Spermatogenesis
;
Adenosine Triphosphatases/pharmacology*
5.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
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blood
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Animals
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Creatine Kinase
;
blood
;
Energy Metabolism
;
Isoflavones
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pharmacology
;
L-Lactate Dehydrogenase
;
blood
;
Lactic Acid
;
blood
;
Male
;
Mice
;
Random Allocation
;
Soybeans
;
chemistry
;
Succinate Dehydrogenase
;
blood
;
Swimming
6.Effects of cocaine on activities of ATPase, LDH and SDH in mouse splenocytes.
Wen-ping SUN ; Yan-xu LU ; Xiao-yu ZHANG ; Wei-wei TANG ; Qing-yu HUANG
Journal of Forensic Medicine 2010;26(2):81-83
OBJECTIVE:
To examine the effects of cocaine on the activities of ATPase, LDH and SDH in cultured mouse splenocytes in vitro.
METHODS:
The ATPase, LDH and SDH activities in mouse splenocytes were detected at day 7 after continuous culturing the mouse cells exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL in vitro.
RESULTS:
The activities of ATPase, LDH and SDH in mouse splenocytes exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL were significantly decreased after continuous culturing for 7 days.
CONCLUSION
The present study demonstrated that cocaine could inhibit the activities of ATPase, LDH and SDH in cultured splenocytes in vitro.
Adenosine Triphosphatases/metabolism*
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Animals
;
Cells, Cultured
;
Cocaine/pharmacology*
;
Dose-Response Relationship, Drug
;
L-Lactate Dehydrogenase/metabolism*
;
Male
;
Mice
;
Mice, Inbred Strains
;
Spleen/enzymology*
;
Succinate Dehydrogenase/metabolism*
7.Recent advance in the mechanism study of polymeric inhibitors of P-glycoprotein.
Lei-ming HUANG ; Jin-hua ZHAO ; Guo-cheng WANG ; Jian-ping ZHOU
Acta Pharmaceutica Sinica 2010;45(10):1224-1231
P-glycoprotein (P-gp) is an ATP-dependent multidrug efflux pump that acts as a major obstacle for oral drug delivery and cancer therapy. Recent reports have provided evidence that excipients often used in pharmaceutical formulations, such as Pluronic and TPGS, also have inhibitory effects on P-glycoprotein. Because inhibition of efflux transporters by polymeric inhibitors may dramatically increase the bioavailability of P-gp substrates with negligible side effects, identification of the mechanism and their structure activity relationship is therefore of significant importance for pharmaceutical development. Other than competitive inhibition for traditional inhibitors, polymeric inhibitors may modify P-gp function through alterations on membrane fluidity, inhibition of P-gp ATPase, depletion of intracellular ATP and down-regulating of P-gp expression. In the present review, the inhibition mechanism of potential polymeric inhibitors and their structure activity relationship will be discussed along with a brief introduction to the established methodologies.
ATP-Binding Cassette, Sub-Family B, Member 1
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antagonists & inhibitors
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chemistry
;
genetics
;
metabolism
;
Adenosine Triphosphatases
;
metabolism
;
Adenosine Triphosphate
;
metabolism
;
Animals
;
Biological Availability
;
Excipients
;
pharmacology
;
Gene Expression
;
Humans
;
Membrane Fluidity
;
drug effects
;
Polymers
;
pharmacology
;
Structure-Activity Relationship
8.Injury of mouse brain mitochondria induced by cigarette smoke extract and effect of vitamin C on it in vitro.
Biomedical and Environmental Sciences 2003;16(3):256-266
OBJECTIVETo investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro.
METHODMouse brain mitochondria in vitro was incubated with CSE or nicotine in the absence or presence of vitamin C for 60 minutes, and the changes of mitochondrial function and structure were measured.
RESULTSCSE inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. However, no significant changes in the peroxidation indices were observed when mitochondrial respiratory enzymes activity was inhibited, and protection of mitochondria from CSE-induced injury by vitamin C was not displayed in vitro. The effect of CSE on mouse brain mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. CSE inhibited swelling of mitochondria at 6.5 mumol/L Ca2+, but promoted swelling response at 250 mumol/L Ca2+. Nicotine, the major component of cigarette smoke, showed no significant damage in mouse brain mitochondria in vitro. The CSE treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane appeared to be preserved.
CONCLUSIONThe toxic effect of CSE on brain mitochondria may be due to its direct action on enzymatic activity rather than through oxygen free radical injury. Nicotine is not the responsible component for the toxicity of CSE to brain mitochondria.
Adenosine Triphosphatases ; pharmacology ; Animals ; Antioxidants ; pharmacology ; Ascorbic Acid ; pharmacology ; Brain ; pathology ; Electron Transport Complex IV ; pharmacology ; Free Radicals ; Ganglionic Stimulants ; toxicity ; Mice ; Mitochondria ; pathology ; Nicotine ; toxicity ; Smoke ; adverse effects ; Tobacco
9.Effects of NBP on ATPase and anti-oxidant enzymes activities and lipid peroxidation in transient focal cerebral ischemic rats.
Acta Academiae Medicinae Sinicae 2002;24(1):93-97
OBJECTIVEThe aim of the present study was designed to explore the effect of (+/-) -3-n-butylphthalide (NBP) on ATPase, anti-oxidant enzymes activities and lipid peroxidation of mitochondria and cerebral cortex in rats subjected to 24 hours of reperfusion following 2 hours of cerebral ischemia (tMCAO).
METHODSActivities of SOD (Superoxide Dismutase), GSH-Px (glutathione Peroxidase,) and CAT (Catalase), and MDA level of mitochondria or cortex were measured by using biochemical methods in tMCAO rats.
RESULTS(1) The activities of mitochondrial Na+K(+)-ATPase, Ca(2+)-ATPase and Mg2+ ATPase were found to decrease significantly in the vehicle group (ischemia + saline). Pre-treatment with NBP (5, 10, 20 mg/kg, i.p.) 10 min before tMCAO markedly enhanced the activities of Na+K(+)-ATPase and Ca(2+)-ATPase, compared with vehicle group. (2) The activities of SOD and mitochondrial GSH-Px were decreased and MDA level increased in vehicle groups as compared with that in sham group (non-ischemia + saline). NBP (20 mg/kg, i.p.) significantly enhanced total mitochondrial SOD activity, and also enhanced cerebral cortex total SOD activity (in 5, 10, 20 mg/kg groups). However, it had no obvious effect on CuZn-SOD activity. NBP (20 mg/kg i.p.) markedly increased mitochondrial (but not in cerebral cortex) GSH-Px activity; NBP 10, 20 mg/kg markedly decreased mitochondrial MDA level compared with that in vehicle group (P < 0.05). (3) The action of raceme NBP on the increase of the activities of ATPase and antioxidative enzymes seemed to be beneficial than that of (-) -NBP or (+) NBP.
CONCLUSIONThe results suggest that NBP improves energy pump and subsides oxidative injury which may contribute to its anti-neuronal apoptotic effect.
Adenosine Triphosphatases ; metabolism ; Animals ; Benzofurans ; pharmacology ; Cerebral Cortex ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Glutathione Peroxidase ; metabolism ; Ischemic Attack, Transient ; enzymology ; Lipid Peroxidation ; Male ; Mitochondria ; enzymology ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Wistar ; Reperfusion Injury ; enzymology ; Superoxide Dismutase ; metabolism
10.Effects of salvianolic acid B on cerebral energy charge and activity of ATPase in mice with cerebral ischemia.
Yu-Feng JIANG ; Qiu-Hua WANG ; Zhi-Qin LIU ; Qian WANG ; Da-Yong CAI ; Shi-Jing LIU ; Ying ZHANG ; Qi-Fu HUANG
China Journal of Chinese Materia Medica 2007;32(18):1903-1906
OBJECTIVETo observe the effect of salvianolic acid B (SalB) on high energy phosphate and activity of ATPase of cerebral ischemia in mice, and to study the role of SalB on hydrocephalus further.
METHODNIH mice were divided into four groups randomly: Sham-operated group, cerebral ischemia group, SalB-treated group and Nimodipine (Nim)-collated group. In Sal B-treated group, mice were injected with SalB (22.5 mg x kg(-1)) in vena caudalis at 30 min before the experiment. In Nim-collated group, Nim (0.03 mg x kg(-1)) was injected into tail vein at the same time, while the mice in Sham-operated group and cerebral ischemia group were injected the same volume normal saline. The acute cerebral ischemia model was established by ligating bilateral common carotid arteries for 30 min in mice, then the mice were killed and the content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphocreatine (PCr) were observed, and the cerebral energy charge (EC) was computed. At the same time, activity of Na(+) -K(+) -ATPase and Ca2(+) -ATPase, content of water in brain tissue were measured.
RESULTCompared with cerebral ischemia group, EC and content of ATP, ADP, PCr in SalB-treated group heightened evidently (P < 0.01). Moreover, activity of Na(+)-K+ ATPase and Ca2+ ATPase in SalB-treated group had a remarkable increase (P < 0.01). But the content of water in brain tissue decreased markedly (P < 0.05).
CONCLUSIONThe mechanism that SalB can relieve content of water in brain tissue of cerebral ischemia in mice, may be associated with improving the content of high-energy phosphoric acid compounds and enhancing the activity of ATPase.
Adenosine Diphosphate ; metabolism ; Adenosine Monophosphate ; metabolism ; Adenosine Triphosphatases ; metabolism ; Adenosine Triphosphate ; metabolism ; Animals ; Benzofurans ; isolation & purification ; pharmacology ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; physiopathology ; Calcium-Transporting ATPases ; metabolism ; Energy Metabolism ; drug effects ; Male ; Mice ; Phosphocreatine ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Salvia miltiorrhiza ; chemistry ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Water ; metabolism