Frontiers in Clinical Drug Research: Hematology

Volume: 3

Erythrocyte Turnover and Erythropoietic Patterns in Two Different Experimental Mouse Models of Anemia

Author(s): Sreoshi Chatterjee and Rajiv K. Saxena

Pp: 220-251 (32)

DOI: 10.2174/9781681083674118030008

* (Excluding Mailing and Handling)

Abstract

Murine models of cadmium induced anemia (50 ppm and 1000 ppm CdCl2 in drinking water) and autoimmune hemolytic anemia (AIHA) were compared to gain a holistic understanding of the modulation of erythroid homeostasis in anemia. Our results indicated completely contrasting changes in the modulation of erythroid homeostasis in the two forms of anemia. The novel DIB (double in vivo biotinylation) technique developed in our laboratory revealed that older erythrocytes with significantly high level of intracellular reactive oxygen species (ROS) were preferentially more prone to elimination in CdCl2 fed mice, indicated by a significant decline in the relative proportions of older erythrocytes along with a concomitant increase in the proportion of young erythrocytes in circulation. On the contrary, in mice with induced AIHA, selective susceptibility of younger erythrocytes was observed, with more autoantibody binding and highest accumulation of intracellular ROS. Cadmium exposure resulted in a significant yet transient reticulocytosis, whereas an acute reticulocytopenia was observed in autoimmune anemia. Erythropoietic activity in the bone marrows (BM) and the spleen of anemic mice were examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Results indicate a suppressed BM erythropoietic activity in both the models of anemia. In cadmium-induced anemia the early erythroid precursors (proerythroblasts) suffered the maximum, while in AIHA-induced mice the later stages of erythroid differentiation (erythroblasts C) were affected the most (50% decline). These populations also showed high intracellular ROS level along with enhanced apoptotic response. A stress erythropoietic response in spleen was seen in mice with induced AIHA, which was however absent in cadmium induced anemia (though increased erythropoietic activity in the early stages of differentiation was evident in spleen).


Keywords: Anemia, Autoimmune hemolytic anemia, Autoantibody, Cadmium, Double in vivo biotinylation, Erythrocyte turnover, Erythropoiesis, Flow cytometry, Mouse models of anemia, Reactive oxygen species.

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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 221938058 and j.to_ip >=221938058 )) and ((j.from_date <= 1740456326 and j.to_date >= 1740456326 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12037) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 221938058 and j.to_ip >=221938058 )) and ((j.from_date <= 1740456326 and j.to_date >= 1740456326 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12037) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 221938058 and j.to_ip >=221938058 )) and ((j.from_date <= 1740456326 and j.to_date >= 1740456326 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12037)
      640μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 2438 and `b`.`banner_from_date` <= 1740456326 and `b`.`banner_to_date` >= 1740456326 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.1msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2438
      • 3: 1740456326
      • 4: 1740456326
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='491cab827816b2cdf3194f75d2f3fe73'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    10Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        41Kd4jx49XHQrdA2OtrAPIGWe20JN008KfbOQLQt
        uc_cart_id
        491cab827816b2cdf3194f75d2f3fe73
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/12037" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/12037
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 04:05:26 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlEyUlN4YWFZTU1GZmcxRTY4TTcxenc9PSIsInZhbHVlIjoiMkYyYnJDL0VWRy9TaUxaM0FMRE5iWHFUd3pCaVlqVkFBbXRsZjVRaEY2dmVPeFBablh2eFlieGxiczBVNnlsYUsvNFdTb0FMNXdKVytiR284WWhndDVpT0hzYytrV3lIVHRXb0UzbHRoUHhwZ2txM3RPSjhMOHRIY0M0RC91cWQiLCJtYWMiOiI4OTA2MDY4M2VmZTExOTM4N2RjOTNiOGU3NTExOTJkNDNmMmJhNTMxNGIxYzMyODVjYTNlZTIxODgzNjBlMmVlIiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 16:05:26 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlEyUlN4YWFZTU1GZmcxRTY4TTcxenc9PSIsInZhbHVlIjoiMkYyYnJDL0VWRy9TaUxaM0FMRE5iWHFUd3pCaVlqVkFBbXRsZjVRaEY2dmVPeFBablh2eFlieGxiczBVNnlsYUsvNFdTb" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlhZVFpydStvUVFTN2JvdkVvcW1CYlE9PSIsInZhbHVlIjoiMjhHVFE1TElJVjIrNTNhL1hmWEF3NE0yYzBoYURHWWZOa1dqRC82VFBnc2Vwc1VhRzRLbmdTelcvVjZWVUxjbW03M0xBRW1EUkJSUnBhaklha202OUNUSCtPTDBMZGJJZG05TGYwRTNwUjk2dkNRbUljWHJGczFDU21DN0IyNHEiLCJtYWMiOiJkNGE4N2Q1YTA2NGI0MjJiOWIxNWFjYjc0MjUyMjhlNmVlZGFkZDMzY2Y2MjgyNTE0ODk5NjE2ODdkOWQ4YjBhIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlhZVFpydStvUVFTN2JvdkVvcW1CYlE9PSIsInZhbHVlIjoiMjhHVFE1TElJVjIrNTNhL1hmWEF3NE0yYzBoYURHWWZOa1dqRC82VFBnc2Vwc1VhRzRLbmdTelc" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlEyUlN4YWFZTU1GZmcxRTY4TTcxenc9PSIsInZhbHVlIjoiMkYyYnJDL0VWRy9TaUxaM0FMRE5iWHFUd3pCaVlqVkFBbXRsZjVRaEY2dmVPeFBablh2eFlieGxiczBVNnlsYUsvNFdTb0FMNXdKVytiR284WWhndDVpT0hzYytrV3lIVHRXb0UzbHRoUHhwZ2txM3RPSjhMOHRIY0M0RC91cWQiLCJtYWMiOiI4OTA2MDY4M2VmZTExOTM4N2RjOTNiOGU3NTExOTJkNDNmMmJhNTMxNGIxYzMyODVjYTNlZTIxODgzNjBlMmVlIiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 16:05:26 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlEyUlN4YWFZTU1GZmcxRTY4TTcxenc9PSIsInZhbHVlIjoiMkYyYnJDL0VWRy9TaUxaM0FMRE5iWHFUd3pCaVlqVkFBbXRsZjVRaEY2dmVPeFBablh2eFlieGxiczBVNnlsYUsvNFdTb" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlhZVFpydStvUVFTN2JvdkVvcW1CYlE9PSIsInZhbHVlIjoiMjhHVFE1TElJVjIrNTNhL1hmWEF3NE0yYzBoYURHWWZOa1dqRC82VFBnc2Vwc1VhRzRLbmdTelcvVjZWVUxjbW03M0xBRW1EUkJSUnBhaklha202OUNUSCtPTDBMZGJJZG05TGYwRTNwUjk2dkNRbUljWHJGczFDU21DN0IyNHEiLCJtYWMiOiJkNGE4N2Q1YTA2NGI0MjJiOWIxNWFjYjc0MjUyMjhlNmVlZGFkZDMzY2Y2MjgyNTE0ODk5NjE2ODdkOWQ4YjBhIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlhZVFpydStvUVFTN2JvdkVvcW1CYlE9PSIsInZhbHVlIjoiMjhHVFE1TElJVjIrNTNhL1hmWEF3NE0yYzBoYURHWWZOa1dqRC82VFBnc2Vwc1VhRzRLbmdTelc" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "41Kd4jx49XHQrdA2OtrAPIGWe20JN008KfbOQLQt" "uc_cart_id" => "491cab827816b2cdf3194f75d2f3fe73" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/chapter/12037" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 04:05:26GET/chapter/120371121912