Doxycycline Hyclate Modulates Antioxidant Defenses, Matrix Metalloproteinases, and COX-2 Activity Accelerating Skin Wound Healing by Secondary Intention in Rats

<div>Immunohistochemical detection of cyclooxygenase-2 (COX-2) in the epithelial cells (a), COX-2 activity (b), prostaglandin E2 (PGE2) levels (c), and N-acetyl-<i>β</i>-D-glucosaminidase (NAG) activity (d) in the scar tissue from rats untreated and treated with doxycycline hyclate (Dx). Cim: control of the immunohistochemical method (the primary antibody was omitted in the technique), C: control, <span class="nowrap"><svg height="12.7112pt" id="M50" style="vertical-align:-3.403299pt" version="1.1" viewbox="-0.0498162 -9.3079 97.8617 12.7112" width="97.8617pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.464,0)"><path d="M474 0V26C414 34 401 43 364 100L267 248C300 297 324 332 345 358C381 400 394 405 455 411V437H272V411C316 406 323 401 305 370C287 337 267 306 247 276L188 369C169 397 173 405 215 411V437H16V411C71 404 83 396 114 348L201 212C171 167 144 127 116 92C77 42 66 34 4 26V0H190V26C139 34 136 43 156 77C175 113 198 150 220 183L294 66C311 39 302 31 260 26V0H474Z"></path></g><g transform="matrix(.013,0,0,-0.013,19.29,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,30.553,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g><g transform="matrix(.013,0,0,-0.013,36.793,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,45.208,0)"><path d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"></path></g><g transform="matrix(.013,0,0,-0.013,55.751,0)"><path d="M463 437C426 431 375 425 327 422C297 440 264 449 231 449H230C153 449 51 396 51 283C51 215 94 168 139 149C123 129 91 103 51 88C50 78 53 60 62 46C75 25 100 2 136 -9C112 -28 73 -59 53 -79C38 -94 29 -113 29 -135C30 -192 91 -257 203 -257C336 -257 452 -160 452 -59C452 39 371 59 309 59C275 59 240 58 203 58C158 58 140 77 140 96C140 110 157 129 170 138C186 135 205 133 221 133C306 133 396 185 396 293C396 328 384 360 366 381L423 378C439 387 459 413 468 429L463 437ZM219 418C277 418 314 362 314 284C314 205 275 166 231 165C176 165 137 221 137 299C137 376 177 418 219 418ZM241 -11C285 -11 314 -14 339 -24C367 -36 384 -61 384 -95C384 -157 335 -206 240 -206C166 -206 108 -165 108 -110C108 -82 128 -54 154 -32C172 -17 195 -11 241 -11Z"></path></g><g transform="matrix(.013,0,0,-0.013,61.898,0)"><path d="M368 703H309L44 -163H104L368 703Z"></path></g><g transform="matrix(.013,0,0,-0.013,67.259,0)"><path d="M513 0V26C475 28 448 43 413 81C379 116 277 234 258 264C301 314 319 334 344 359C383 396 404 407 473 418V443L269 434V408C317 403 320 395 299 364C280 337 250 298 228 276C213 260 195 247 165 241V712C126 699 69 682 21 677V653C82 648 87 642 87 576V104C87 40 81 32 14 26V0H237V26C173 32 165 38 165 104V215C171 217 176 218 181 218C189 218 198 212 212 196C267 129 330 49 376 -2L513 0Z"></path></g><g transform="matrix(.013,0,0,-0.013,73.707,0)"><path d="M463 437C426 431 375 425 327 422C297 440 264 449 231 449H230C153 449 51 396 51 283C51 215 94 168 139 149C123 129 91 103 51 88C50 78 53 60 62 46C75 25 100 2 136 -9C112 -28 73 -59 53 -79C38 -94 29 -113 29 -135C30 -192 91 -257 203 -257C336 -257 452 -160 452 -59C452 39 371 59 309 59C275 59 240 58 203 58C158 58 140 77 140 96C140 110 157 129 170 138C186 135 205 133 221 133C306 133 396 185 396 293C396 328 384 360 366 381L423 378C439 387 459 413 468 429L463 437ZM219 418C277 418 314 362 314 284C314 205 275 166 231 165C176 165 137 221 137 299C137 376 177 418 219 418ZM241 -11C285 -11 314 -14 339 -24C367 -36 384 -61 384 -95C384 -157 335 -206 240 -206C166 -206 108 -165 108 -110C108 -82 128 -54 154 -32C172 -17 195 -11 241 -11Z"></path></g><g transform="matrix(.013,0,0,-0.013,82.013,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,91.477,0)"><path d="M474 0V26C414 34 401 43 364 100L267 248C300 297 324 332 345 358C381 400 394 405 455 411V437H272V411C316 406 323 401 305 370C287 337 267 306 247 276L188 369C169 397 173 405 215 411V437H16V411C71 404 83 396 114 348L201 212C171 167 144 127 116 92C77 42 66 34 4 26V0H190V26C139 34 136 43 156 77C175 113 198 150 220 183L294 66C311 39 302 31 260 26V0H474Z"></path></g></svg>,</span> and <span class="nowrap"><svg height="12.7112pt" id="M51" style="vertical-align:-3.403299pt" version="1.1" viewbox="-0.0498162 -9.3079 104.125 12.7112" width="104.125pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,9.464,0)"><path d="M474 0V26C414 34 401 43 364 100L267 248C300 297 324 332 345 358C381 400 394 405 455 411V437H272V411C316 406 323 401 305 370C287 337 267 306 247 276L188 369C169 397 173 405 215 411V437H16V411C71 404 83 396 114 348L201 212C171 167 144 127 116 92C77 42 66 34 4 26V0H190V26C139 34 136 43 156 77C175 113 198 150 220 183L294 66C311 39 302 31 260 26V0H474Z"></path></g><g transform="matrix(.013,0,0,-0.013,15.658,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"></path></g><g transform="matrix(.013,0,0,-0.013,25.53,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,36.793,0)"><path d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"></path></g><g transform="matrix(.013,0,0,-0.013,43.034,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.449,0)"><path d="M797 0V26C739 32 732 36 732 103V296C732 394 682 449 605 449C576 449 550 437 529 423C504 407 475 389 446 366C425 418 382 449 334 449C303 449 279 437 253 421C222 403 201 385 180 371V452C135 432 85 419 41 411V388C99 379 102 374 102 310V103C102 38 93 32 27 26V0H238V26C189 32 180 38 180 103V338C210 363 250 390 289 390C351 390 377 348 377 275V103C377 37 368 32 306 26V0H520V26C465 32 456 38 456 101V296C456 314 455 326 453 338C491 369 529 390 565 390C628 390 653 345 653 274V107C653 36 642 32 583 26V0H797Z"></path></g><g transform="matrix(.013,0,0,-0.013,61.991,0)"><path d="M463 437C426 431 375 425 327 422C297 440 264 449 231 449H230C153 449 51 396 51 283C51 215 94 168 139 149C123 129 91 103 51 88C50 78 53 60 62 46C75 25 100 2 136 -9C112 -28 73 -59 53 -79C38 -94 29 -113 29 -135C30 -192 91 -257 203 -257C336 -257 452 -160 452 -59C452 39 371 59 309 59C275 59 240 58 203 58C158 58 140 77 140 96C140 110 157 129 170 138C186 135 205 133 221 133C306 133 396 185 396 293C396 328 384 360 366 381L423 378C439 387 459 413 468 429L463 437ZM219 418C277 418 314 362 314 284C314 205 275 166 231 165C176 165 137 221 137 299C137 376 177 418 219 418ZM241 -11C285 -11 314 -14 339 -24C367 -36 384 -61 384 -95C384 -157 335 -206 240 -206C166 -206 108 -165 108 -110C108 -82 128 -54 154 -32C172 -17 195 -11 241 -11Z"></path></g><g transform="matrix(.013,0,0,-0.013,68.138,0)"><path d="M368 703H309L44 -163H104L368 703Z"></path></g><g transform="matrix(.013,0,0,-0.013,73.499,0)"><path d="M513 0V26C475 28 448 43 413 81C379 116 277 234 258 264C301 314 319 334 344 359C383 396 404 407 473 418V443L269 434V408C317 403 320 395 299 364C280 337 250 298 228 276C213 260 195 247 165 241V712C126 699 69 682 21 677V653C82 648 87 642 87 576V104C87 40 81 32 14 26V0H237V26C173 32 165 38 165 104V215C171 217 176 218 181 218C189 218 198 212 212 196C267 129 330 49 376 -2L513 0Z"></path></g><g transform="matrix(.013,0,0,-0.013,79.947,0)"><path d="M463 437C426 431 375 425 327 422C297 440 264 449 231 449H230C153 449 51 396 51 283C51 215 94 168 139 149C123 129 91 103 51 88C50 78 53 60 62 46C75 25 100 2 136 -9C112 -28 73 -59 53 -79C38 -94 29 -113 29 -135C30 -192 91 -257 203 -257C336 -257 452 -160 452 -59C452 39 371 59 309 59C275 59 240 58 203 58C158 58 140 77 140 96C140 110 157 129 170 138C186 135 205 133 221 133C306 133 396 185 396 293C396 328 384 360 366 381L423 378C439 387 459 413 468 429L463 437ZM219 418C277 418 314 362 314 284C314 205 275 166 231 165C176 165 137 221 137 299C137 376 177 418 219 418ZM241 -11C285 -11 314 -14 339 -24C367 -36 384 -61 384 -95C384 -157 335 -206 240 -206C166 -206 108 -165 108 -110C108 -82 128 -54 154 -32C172 -17 195 -11 241 -11Z"></path></g><g transform="matrix(.013,0,0,-0.013,88.254,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,97.717,0)"><path d="M474 0V26C414 34 401 43 364 100L267 248C300 297 324 332 345 358C381 400 394 405 455 411V437H272V411C316 406 323 401 305 370C287 337 267 306 247 276L188 369C169 397 173 405 215 411V437H16V411C71 404 83 396 114 348L201 212C171 167 144 127 116 92C77 42 66 34 4 26V0H190V26C139 34 136 43 156 77C175 113 198 150 220 183L294 66C311 39 302 31 260 26V0H474Z"></path></g></svg>.</span> In the graphics, data are represented as mean and standard deviation. <svg height="10.1524pt" id="M52" style="vertical-align:-0.04990005pt" version="1.1" viewbox="-0.0498162 -10.1025 6.17869 10.1524" width="6.17869pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z"></path></g></svg>Statistical difference compared to group C (Student-Newman-Keuls test, <span class="nowrap"><svg height="11.7782pt" id="M53" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"></path></g></svg>).</span></div>

Oxidative Medicine and Cellular Longevity

fig8

Figure 8

Figure 8: Doxycycline Hyclate Modulates Antioxidant Defenses, Matrix Metalloproteinases, and COX-2 Activity Accelerating Skin Wound Healing by Secondary Intention in Rats 

Figure 8 | Doxycycline Hyclate Modulates Antioxidant Defenses, Matrix Metalloproteinases, and COX-2 Activity Accelerating Skin Wound Healing by Secondary Intention in Rats 